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  • 1.
    Alvarez-Rodriguez, Manuel
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Ntzouni, Maria
    Linköping University, Faculty of Medicine and Health Sciences, Core Facility.
    Wright, Dominic
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Khan, Kabirul Islam
    Chattogram Vet and Anim Sci Univ, Bangladesh.
    Lopez-Bejar, Manel
    Univ Autonoma Barcelona, Spain.
    Martinez-Serrano, Cristina
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Rodriguez-Martinez, Heriberto
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Chicken seminal fluid lacks CD9-and CD44-bearing extracellular vesicles2020In: Reproduction in domestic animals, ISSN 0936-6768, E-ISSN 1439-0531, Vol. 55, no 3, p. 293-300Article in journal (Refereed)
    Abstract [en]

    The avian seminal fluid (SF) is a protein-rich fluid, derived from the testis, the rudimentary epididymis and, finally, from the cloacal gland. The SF interacts with spermatozoa and the inner cell lining of the female genital tract, to modulate sperm functions and female immune responsiveness. Its complex proteome might either be free or linked to extracellular vesicles (EVs) as it is the case in mammals, where EVs depict the tetraspanin CD9; and where those EVs derived from the epididymis (epididymosomes) also present the receptor CD44. In the present study, sperm-free SF from Red Jungle Fowl, White Leghorn and an advanced intercross (AIL, 12th generation) were studied using flow cytometry of the membrane marker tetraspanin CD9, Western blotting of the membrane receptor CD44 and electron microscopy in non-enriched (whole SF) or enriched fractions obtained by precipitation using a commercial kit (Total Exosome Precipitation Solution). Neither CD9- nor CD44 could be detected, and the ultrastructure confirmed the relative absence of EVs, raising the possibility that avian SF interacts differently with the female genitalia as compared to the seminal plasma of mammals.

  • 2.
    Ansell, Ricky
    et al.
    Swedish National Forensic Centre, Linköping, Sweden.
    Allen, Marie
    Molekylär patologi och rättsgenetik, Uppsala universitet.
    DNA-analyser inom brottsbekämpningen2016In: Skurk, sjuk eller släkt?: vem ska ha ditt DNA? / [ed] Eva Regårdh, Sofie Pehrssoon, Stockholm: Stiftelsen för strategisk forskning , 2016, p. 18-27Chapter in book (Other academic)
    Abstract [sv]

    Idag räcker det med DNA från enstaka celler för att kunna få fram en DNA-profil som kan jämföras med per-soner eller andra DNA-spår. En DNA-träff mot ett biologiskt spår kan utgöra en mycket stark bevisning och vara avgörande för en fällande dom. DNA-teknik gör det möjligt att analysera och ta fram en DNA-profil för de allra flesta typer av humana biologiska spår som avsatts i samband med brott, såsom blod, sperma, vaginalsekret, saliv, hår och ”kontaktspår”. Teknikerna har med åren utvecklats och förfinats. På senare år har också det internationella utbytet av DNA-profiler ökat samtidigt som fortsatt teknik- och metodutveckling banar väg för fördjupade analy-ser som kan bidra till att klara upp brott. Det kan handla om att utifrån DNA-spår ringa in ungefärlig ålder, ursprung, hårfärg, ögonfärg och kroppsstorlek på en misstänkt gärningsman

  • 3.
    Arja, Katriann
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Elgland, Mathias
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Nilsson, Peter
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Synthesis and Characterization of Oligothiophene-Porphyrin-Based Molecules That Can Be Utilized for Optical Assignment of Aggregated Amyloid-beta Morphotypes2018In: Frontiers in Chemistry, E-ISSN 2296-2646, Vol. 6, article id 391Article in journal (Refereed)
    Abstract [en]

    Molecular tools for fluorescent imaging of protein aggregates are essential for understanding the significance of these pathological hallmarks in proteopathic neurodegenerative diseases, such as Alzheimers disease. Here, we report the synthesis of a series of oligothiophene porphyrin hybrids, OTPHs, and the evaluation of these dyes for fluorescent imaging of beta-amyloid aggregates in tissue sections from a transgenic mouse model with Alzheimers disease pathology. The OTPHs proved to be successful for spectral and lifetime imaging assessment of protein deposits and our findings confirm that the enhanced spectral range and distinct lifetime diversity of these novel tools allow a more precise assessment of heterogeneous amyloid morphology compared with the corresponding oligothiophene dye. In addition, the chemical identity of the porphyrin moiety, as well as the spacing between the two optical active moieties, influenced the OTPHs performance for fluorescent assignment of the protein deposits. We foresee that our findings will aid in the chemical design of dyes that can be utilized as optical tools for studying the polymorphic nature of protein aggregates associated with proteopathic neurodegenerative diseases.

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  • 4. Order onlineBuy this publication >>
    Aronsson, Christopher
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Tunable and modular assembly of polypeptides and polypeptide-hybrid biomaterials2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Biomaterials are materials that are specifically designed to be in contact with biological systems and have for a long time been used in medicine. Examples of biomaterials range from sophisticated prostheses used for replacing outworn body parts to ordinary contact lenses. Currently it is possible to create biomaterials that can e.g. specifically interact with cells or respond to certain stimuli. Peptides, the shorter version of proteins, are excellent molecules for fabrication of such biomaterials. By following and developing design rules it is possible to obtain peptides that can self-assemble into well-defined nanostructures and biomaterials.

    The aim of this thesis is to create ”smart” and tunable biomaterials by molecular self-assembly using dimerizing –helical polypeptides. Two different, but structurally related, polypeptide-systems have been used in this thesis. The EKIV-polypeptide system was developed in this thesis and consists of four 28-residue polypeptides that can be mixed-and-matched to self-assemble into four different coiled coil heterodimers. The dissociation constant of the different heterodimers range from μM to < nM. Due to the large difference in affinities, the polypeptides are prone to thermodynamic social self-sorting. The JR-polypeptide system, on the other hand, consists of several 42-residue de novo designed helix-loop-helix polypeptides that can dimerize into four-helix bundles. In this work, primarily the glutamic acid-rich polypeptide JR2E has been explored as a component in supramolecular materials. Dimerization was induced by exposing the polypeptide to either Zn2+, acidic conditions or the complementary polypeptide JR2K.

    By conjugating JR2E to hyaluronic acid and the EKIV-polypeptides to star-shaped poly(ethylene glycol), respectively, highly tunable hydrogels that can be self-assembled in a modular fashion have been created. In addition, self-assembly of spherical superstructures has been investigated and were obtained by linking two thiol-modified JR2E polypeptides via a disulfide bridge in the loop region. ŒThe thesis also demonstrates that the polypeptides and the polypeptide-hybrids can be used for encapsulation and release of molecules and nanoparticles. In addition, some of the hydrogels have been explored for 3D cell culture. By using supramolecular interactions combined with bio-orthogonal covalent crosslinking reactions, hydrogels were obtained that enabled facile encapsulation of cells that retained high viability.

    The results of the work presented in this thesis show that dimerizing α–helical polypeptides can be used to create modular biomaterials with properties that can be tuned by specific molecular interactions. The modularity and the tunable properties of these smart biomaterials are conceptually very interesting andmake them useful in many emerging biomedical applications, such as 3D cell culture, cell therapy, and drug delivery

    .

    List of papers
    1. Self-sorting heterodimeric coiled coil peptides with defined and tuneable self-assembly properties
    Open this publication in new window or tab >>Self-sorting heterodimeric coiled coil peptides with defined and tuneable self-assembly properties
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    2015 (English)In: Scientific Reports, E-ISSN 2045-2322, Vol. 5, no 14063Article in journal (Refereed) Published
    Abstract [en]

    Coiled coils with defined assembly properties and dissociation constants are highly attractive components in synthetic biology and for fabrication of peptide-based hybrid nanomaterials and nanostructures. Complex assemblies based on multiple different peptides typically require orthogonal peptides obtained by negative design. Negative design does not necessarily exclude formation of undesired species and may eventually compromise the stability of the desired coiled coils. This work describe a set of four promiscuous 28-residue de novo designed peptides that heterodimerize and fold into parallel coiled coils. The peptides are non-orthogonal and can form four different heterodimers albeit with large differences in affinities. The peptides display dissociation constants for dimerization spanning from the micromolar to the picomolar range. The significant differences in affinities for dimerization make the peptides prone to thermodynamic social self-sorting as shown by thermal unfolding and fluorescence experiments, and confirmed by simulations. The peptides self-sort with high fidelity to form the two coiled coils with the highest and lowest affinities for heterodimerization. The possibility to exploit self-sorting of mutually complementary peptides could hence be a viable approach to guide the assembly of higher order architectures and a powerful strategy for fabrication of dynamic and tuneable nanostructured materials.

    Place, publisher, year, edition, pages
    NATURE PUBLISHING GROUP, 2015
    National Category
    Physical Sciences Electrical Engineering, Electronic Engineering, Information Engineering
    Identifiers
    urn:nbn:se:liu:diva-121739 (URN)10.1038/srep14063 (DOI)000361177400001 ()26370878 (PubMedID)
    Note

    Funding Agencies|Swedish Research Council (VR); Swedish Foundation for Strategic Research (SSF)

    Available from: 2015-10-06 Created: 2015-10-05 Last updated: 2022-09-15
    2. Tailoring Supramolecular Peptide-Poly(ethylene glycol) Hydrogels by Coiled Coil Self-Assembly and Self-Sorting
    Open this publication in new window or tab >>Tailoring Supramolecular Peptide-Poly(ethylene glycol) Hydrogels by Coiled Coil Self-Assembly and Self-Sorting
    2016 (English)In: Biomacromolecules, ISSN 1525-7797, E-ISSN 1526-4602, Vol. 17, no 6, p. 2260-2267Article in journal (Refereed) Published
    Abstract [en]

    Physical hydrogels are extensively used in a wide range of biomedical applications. However, different applications require hydrogels with different mechanical and structural properties. Tailoring these properties demands exquisite control over the supramolecular peptides with different affinities for dimerization. Four different mechanical properties of hydrogels using de novo designed coiled coil interactions involved. Here we show that it is possible to control the nonorthogonal peptides, designed to fold into four different coiled coil heterodimers with dissociation constants spanning from mu M to pM, were conjugated to star-shaped 4-arm poly(ethylene glycol) (PEG). The different PEG-coiled coil conjugates self-assemble as a result of peptide heterodimerization. Different combinations of PEG peptide conjugates assemble into PEG peptide networks and hydrogels with distinctly different thermal stabilities, supramolecular, and rheological properties, reflecting the peptide dimer affinities. We also demonstrate that it is possible to rationally modulate the self-assembly process by means of thermodynamic self-sorting by sequential additions of nonpegylated peptides. The specific interactions involved in peptide dimerization thus provides means for programmable and reversible self-assembly of hydrogels with precise control over rheological properties, which can significantly facilitate optimization of their overall performance and adaption to different processing requirements and applications.

    Place, publisher, year, edition, pages
    AMER CHEMICAL SOC, 2016
    National Category
    Polymer Chemistry
    Identifiers
    urn:nbn:se:liu:diva-130135 (URN)10.1021/acs.biomac.6b00528 (DOI)000377924800038 ()27219681 (PubMedID)
    Note

    Funding Agencies|Swedish Research Council [621-2011-4319]; Swedish Foundation for Strategic Research [ICA10-0002]; Linkoping University; Swedish Government Strategic Research Area in Materials Science on Functional Materials at Linkoping University (Faculty Grant SFO-Mat-LiU) [2009 00971]

    Available from: 2016-07-12 Created: 2016-07-11 Last updated: 2019-01-22
    3. Zinc-Triggered Hierarchical Self-Assembly of Fibrous Helix-Loop-Helix Peptide Superstructures for Controlled Encapsulation and Release
    Open this publication in new window or tab >>Zinc-Triggered Hierarchical Self-Assembly of Fibrous Helix-Loop-Helix Peptide Superstructures for Controlled Encapsulation and Release
    2016 (English)In: Macromolecules, ISSN 0024-9297, E-ISSN 1520-5835, Vol. 49, no 18, p. 6997-7003Article in journal (Refereed) Published
    Abstract [en]

    We demonstrate a novel route for hierarchical self-assembly of sub-micrometer-sized peptide superstructures that respond to subtle changes in Zn2+ concentration. The self-assembly process is triggered by a specific folding-dependent coordination of Zn2+ by a de novo designed nonlinear helix-loop-helix peptide, resulting in a propagating fiber formation and formation of spherical superstructures. The superstructures further form larger assemblies that can be completely disassembled upon removal of Zn2+ or degradation of the nonlinear peptide. This flexible and reversible assembly strategy of the superstructures enables facile encapsulation of nanoparticles and drugs that can be released by means of different stimuli.

    Place, publisher, year, edition, pages
    AMER CHEMICAL SOC, 2016
    National Category
    Polymer Chemistry
    Identifiers
    urn:nbn:se:liu:diva-132215 (URN)10.1021/acs.macromol.6b01724 (DOI)000384399100030 ()
    Note

    Funding Agencies|Swedish Research Council [621-2011-4319]; Swedish Foundation for Strategic Research [ICA10-0002]; Linkoping University; Swedish Government Strategic Research Area in Materials Science on Functional Materials at Linkoping University [2009 00971]

    Available from: 2016-10-26 Created: 2016-10-21 Last updated: 2019-01-22
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    Tunable and modular assembly of polypeptides and polypeptide-hybrid biomaterials
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  • 5.
    Azeem, Muhammad
    et al.
    Bahauddin Zakariya Univ, Pakistan; Hamdard Univ Islamabad, Pakistan.
    Hanif, Muhammad
    Bahauddin Zakariya Univ, Pakistan.
    Mahmood, Khalid
    Bahauddin Zakariya Univ, Pakistan.
    Siddique, Farhan
    Linköping University, Department of Science and Technology, Laboratory of Organic Electronics. Linköping University, Faculty of Science & Engineering. Bahauddin Zakariya Univ, Pakistan.
    Hashem, Heba E.
    Ain Shams Univ, Egypt.
    Aziz, Mubashir
    Bahauddin Zakariya Univ, Pakistan.
    Ameer, Nabeela
    Bahauddin Zakariya Univ, Pakistan.
    Abid, Usman
    Bahauddin Zakariya Univ, Pakistan.
    Latif, Hafsa
    Bahauddin Zakariya Univ, Pakistan.
    Ramzan, Nasreen
    Bahauddin Zakariya Univ, Pakistan.
    Rawat, Ravi
    MVN Univ, India.
    Design, synthesis, spectroscopic characterization, in-vitro antibacterial evaluation and in-silico analysis of polycaprolactone containing chitosan-quercetin microspheres2023In: Journal of Biomolecular Structure and Dynamics, ISSN 0739-1102, E-ISSN 1538-0254, Vol. 41, no 15, p. 7084-7103Article in journal (Refereed)
    Abstract [en]

    Aim of present study was to synthesize a novel chitosan-quercetin (CTS-QT) complex by making a carbodiimide linkage using maleic anhydride as cross-linker and to investigate its enhanced antibacterial and antioxidant activities as compare to pure CTS and QT. Equimolar concentration of QT and maleic anhydride were used to react with 100 mg CTS to form CTS-QT complex. For this purpose, three bacterial strains namely E. Coli, S. Aureus and P. Aeruginosa were used for in-vitro antibacterial analysis (ZOI, MIC, MBC, checker board and time kill assay). Later molecular docking studies were performed on protein structure of E. Coli to assess binding affinity of pure QT and CTS-QT complex. MD simulations with accelerated settings were used to explore the protein-ligand complexs binding interactions and stability. Antioxidant profile was determined by performing DPPH center dot radical scavenging assay, total antioxidant capacity (TAC) and total reducing power (TRP) assays. Delivery mechanism to CTS-QT complex was improved by synthesizing polycaprolactone containing microspheres (CTS-QT-PCL-Levo-Ms) using Levofloxacin as model drug to enhance their antibacterial profile. Resulted microspheres were evaluated by particle size, charge, surface morphology, in-vitro drug release and hemolytic profile and are all were found within limits. Antibacterial assay revealed that CTS-QT-PCL-Levo-Ms showed more than two folds increased bactericidal activity against E. Coli and P. Aeruginosa, while 1.5 folds against S. Aureus. Green colored formation of phosphate molybdate complexes with highest 85 +/- 1.32% TAC confirmed its antioxidant properties. Furthermore, molecular docking and dynamics studies revealed that CTS-QT was embedded nicely within the active pocket of UPPS with binding energy greater than QT with RSMD value of below 1.5. Conclusively, use of maleic acid, in-vitro and in-silico antimicrobial studies confirm the emergence of CTS-QT complex containing microspheres as novel treatment strategy for all types of bacterial infections. Communicated by Ramaswamy H. Sarma

  • 6.
    Aziz, Mubashir
    et al.
    Islamia Univ Bahawalpur, Pakistan.
    Ejaz, Syeda Abida
    Islamia Univ Bahawalpur, Pakistan.
    Rehman, Hafiz Muzzammel
    Univ Punjab, Pakistan; Alnoorians Grp Inst, Pakistan.
    Alsubaie, A. S. A.
    Taif Univ, Saudi Arabia.
    Mahmoud, K. H.
    Taif Univ, Saudi Arabia.
    Siddique, Farhan
    Linköping University, Department of Science and Technology, Laboratory of Organic Electronics. Linköping University, Faculty of Science & Engineering. Royal Inst Med Sci Rims, Pakistan.
    Al-Buriahi, M. S.
    Sakarya Univ, Turkey.
    Alrowaili, Z. A.
    Jouf Univ, Saudi Arabia.
    Identification of NEK7 inhibitors: structure based virtual screening, molecular docking, density functional theory calculations and molecular dynamics simulations2023In: Journal of Biomolecular Structure and Dynamics, ISSN 0739-1102, E-ISSN 1538-0254, Vol. 41, no 14, p. 6894-6908Article in journal (Refereed)
    Abstract [en]

    NEK7 is a NIMA related-protein kinase that plays a crucial role in spindle assembly and cell division. Dysregulation of NEK7 protein leads to development and progression of different types of malignancies including colon and breast cancers. Therefore, NEK7 could be considered as an attractive target for anti-cancer drug discovery. However, few efforts have been made for the development of selective inhibitors of NIMA-related kinase but still no FDA approved drug is known to selectively inhibit the NEK7 protein. Dacomitinib and Neratinib are two Enamide derivatives that were approved for treatment against non-small cell lung cancer and breast cancer respectively. Drug repurposing is a time and cost-efficient method for re-evaluating the activities of previously authorized medications. Thus, the present research involves the repurposing of two FDA-approved medications via comprehensive in silico approach including Density functional theory (DFTs) studies which were conducted to determine the electronic properties of the Dacomitinib and Neratinib. Afterward, binding orientation of selected drugs inside NEK7 activation loop was evaluated through molecular docking approach. Selected drugs exhibited potential molecular interactions engaging important amino acid residues of active site. The docking score of Dacomitinib and Neratinib was -30.77 and -26.78 kJ/mol, respectively. The top ranked pose obtained from molecular docking was subjected to Molecular Dynamics (MD) Simulations for investigating the stability of protein-ligand complex. The RMSD pattern revealed the stability of protein-ligand complex throughout simulated trajectory. In conclusion, both drugs displayed inhibitory efficacy against NEK7 protein and provide a prospective therapy option for malignant malignancies linked with NEK7. Communicated by Ramaswamy H. Sarma

  • 7.
    Aziz, Mubashir
    et al.
    Islamia Univ Bahawalpur, Pakistan.
    Ejaz, Syeda Abida
    Islamia Univ Bahawalpur, Pakistan.
    Tamam, Nissren
    Princess Nourah Bint Abdulrahman Univ, Saudi Arabia.
    Siddique, Farhan
    Linköping University, Department of Science and Technology, Laboratory of Organic Electronics. Linköping University, Faculty of Science & Engineering. Royal Inst Med Sci RIMS, Pakistan.
    A comprehensive computational approach for the identification of structure-based potential pharmacological candidates as selective AKR1B1 and AKR1B10 inhibitors: repurposing of purine alkaloids for the treatment of cancer2023In: Journal of Biomolecular Structure and Dynamics, ISSN 0739-1102, E-ISSN 1538-0254, Vol. 41, no 16, p. 7892-7912Article in journal (Refereed)
    Abstract [en]

    Significant metabolic pathways have been linked to AKR1B1 and AKR1B10. These enzymes are crucial biological targets in the therapy of colon cancer. In the past several decades, drug repurposing has gained appeal as a time and cost-efficient strategy for providing new indications for existing drugs. The structural properties of the plant-based alkaloidal drugs theobromine and theophylline were examined using density functional theory (DFT) computations, where the B3LYP/SVP method was used to quantify the dipole moment, polarizability, and optimization energy. Optimized structures obtained through DFT studies were docked inside the active pocket of target proteins to evaluate their inhibitory potential. Moreover, molecular dynamic simulation provides significant insight into a dynamic view of molecular interactions. The findings of current revealed theobromine and theophylline as strong AKR1B1 and AKR1B10 inhibitors, respectively. In addition, the anti-cancer potential of theophylline and theobromine was validated by targeting various tumor proteins, i.e. NF-kappa B, cellular tumor antigen P53 and caspase-3 using a molecular docking approach. Theobromine was found to be strongly interacted with NF-kappa B and caspase-3, whereas theophylline potentially inhibited cellular tumor antigen P53. In addition, the ADMET characteristics of theobromine and theophylline were identified, confirming their drug-like capabilities. These results should open the way for further experimental validation and structure-based drug design/repurposing of AKR1B1/AKR1B10 inhibitors for the treatment of colon cancer and associated malignancies. Communicated by Ramaswamy H. Sarma

  • 8.
    Babu Moparthi, Satish
    et al.
    Aix Marseille University, France.
    Carlsson, Uno
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Vincentelli, Renaud
    University of Aix Marseille, France.
    Jonsson, Bengt-Harald
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Hammarström, Per
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Wenger, Jerome
    Aix Marseille University, France.
    Differential conformational modulations of MreB folding upon interactions with GroEL/ES and TRiC chaperonin components2016In: Scientific Reports, E-ISSN 2045-2322, Vol. 6, no 28386Article in journal (Refereed)
    Abstract [en]

    Here, we study and compare the mechanisms of action of the GroEL/GroES and the TRiC chaperonin systems on MreB client protein variants extracted from E. coli. MreB is a homologue to actin in prokaryotes. Single-molecule fluorescence correlation spectroscopy (FCS) and time-resolved fluorescence polarization anisotropy report the binding interaction of folding MreB with GroEL, GroES and TRiC. Fluorescence resonance energy transfer (FRET) measurements on MreB variants quantified molecular distance changes occurring during conformational rearrangements within folding MreB bound to chaperonins. We observed that the MreB structure is rearranged by a binding-induced expansion mechanism in TRiC, GroEL and GroES. These results are quantitatively comparable to the structural rearrangements found during the interaction of beta-actin with GroEL and TRiC, indicating that the mechanism of chaperonins is conserved during evolution. The chaperonin-bound MreB is also significantly compacted after addition of AMP-PNP for both the GroEL/ES and TRiC systems. Most importantly, our results showed that GroES may act as an unfoldase by inducing a dramatic initial expansion of MreB (even more than for GroEL) implicating a role for MreB folding, allowing us to suggest a delivery mechanism for GroES to GroEL in prokaryotes.

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  • 9. Order onlineBuy this publication >>
    Bergkvist, Liza
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Amyloid-β and lysozyme proteotoxicity in Drosophila: Beneficial effects of lysozyme and serum amyloid P component in models of Alzheimer’s disease and lysozyme amyloidosis2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    In the work presented this thesis, two different conditions that are classified as protein misfolding diseases: Alzheimer's disease and lysozyme amyloidosis and proteins that could have a beneficial effect in these diseases, have been studied using Drosophila melanogaster, commonly known as the fruit fly. The fruit fly has been used for over 100 years to study and better understand fundamental biological processes. Although the fruit fly, unlike humans, is an invertebrate, many of its central biological mechanisms are very similar to ours. The first transgenic flies were designed in the early 1980s, and since then, the fruit fly has been one of the most widely used model organisms in studies on the effects of over-expressed human proteins in a biological system; one can regard the fly as a living, biological test tube. For  most proteins, it is necessary that they fold into a three-dimensional structure to function properly. But sometimes the folding goes wrong; this may be due to mutations that make the protein unstable and subject to misfolding. A misfolded protein molecule can then aggregate with other misfolded proteins. In Alzheimer's disease, which is the most common form of dementia, protein aggregates are present in the brains of patients. These aggregates are composed of the amyloid-β (Aβ) peptide, a small peptide of around 42 amino acids which is cleaved from the larger, membrane-bound, protein AβPP by two different enzymes, BACE1 and γ-secretase. In the first part of this thesis, two different fly models for Alzheimer’s disease were used: the Aβ fly model, which directly expresses the Aβ peptide, and the AβPP-BACE1 fly model, in which all the components necessary to produce the Aβ peptide in the fly are expressed in the fly central nervous system (CNS). The two different fly models were compared and the results show that a significantly smaller amount of the Aβ peptide is needed to achieve the same, or an even greater, toxic effect in the AβPP-BACE1 model compared to the Aβ model. In the second part of the thesis, these two fly models for Alzheimer’s disease were again used, but now to investigate whether lysozyme, a protein involved in our innate immune system, can counteract the toxic effect of Aβ generated in the fly models. And indeed, lysozyme is able to save the flies from Aβ-induced toxicity. Aβ and lysozyme were found to interact with each other in vivo. The second misfolding disease studied in this thesis is lysozyme amyloidosis. It is a rare, dominantly inherited amyloid disease in which mutant variants of lysozyme give rise to aggregates, weighing up to several kilograms, that accumulate around the kidneys and liver, eventually leading to organ failure. In the third part of this thesis, a fly model for lysozyme amyloidosis was used to study the effect of co-expressing the serum amyloid P component (SAP), a protein that is part of all protein aggregates found within this disease class. SAP is able to rescue the toxicity induced by expressing the mutant variant of lysozyme, F57I, in the fly's CNS. To further investigate how SAP was able to do this, double-expressing lysozyme flies, which exhibit stronger disease phenotypes than those of the single-expressing lysozyme flies previously studied, were used in the fourth part of this thesis. SAP was observed to reduce F57I toxicity and promote F57I to form aggregates with more distinct amyloid characteristics. In conclusion, the work included in this thesis demonstrates that: i) Aβ generated from AβPP processing in the fly CNS results in higher proteotoxicity compared with direct expression of Aβ from the transgene, ii) lysozyme can prevent Aβ proteotoxicity in Drosophila and could thus be a potential therapeutic molecule to treat Alzheimer’s disease and iii) in a Drosophila model of lysozyme amyloidosis, SAP can prevent toxicity from the disease-associated lysozyme variant F57I and promote formation of aggregated lysozyme morphotypes with amyloid properties; this is important to take into account when a reduced level of SAP is considered as a treatment strategy for lysozyme amyloidosis.

    List of papers
    1. A beta PP processing results in greater toxicity per amount of A beta(1-42) than individually expressed and secreted A beta(1-42) in Drosophila melanogaster
    Open this publication in new window or tab >>A beta PP processing results in greater toxicity per amount of A beta(1-42) than individually expressed and secreted A beta(1-42) in Drosophila melanogaster
    2016 (English)In: BIOLOGY OPEN, ISSN 2046-6390, Vol. 5, no 8, p. 1030-1039Article in journal (Refereed) Published
    Abstract [en]

    The aggregation of the amyloid-beta (A beta) peptide into fibrillar deposits has long been considered the key neuropathological hallmark of Alzheimers disease (AD). A beta peptides are generated from proteolytic processing of the transmembrane A beta precursor protein (A beta PP) via sequential proteolysis through the beta-secretase activity of beta-site A beta PP-cleaving enzyme (BACE1) and by the intramembranous enzyme gamma-secretase. For over a decade, Drosophila melanogaster has been used as a model organism to study AD, and two different approaches have been developed to investigate the toxicity caused by AD-associated gene products in vivo. In one model, the A beta peptide is directly over-expressed fused to a signal peptide, allowing secretion of the peptide into the extracellular space. In the other model, human A beta PP is co-expressed with human BACE1, resulting in production of the A beta peptide through the processing of A beta PP by BACE1 and by endogenous fly gamma-secretase. Here, we performed a parallel study of flies that expressed the A beta(1-42) peptide alone or that co-expressed A beta PP and BACE1. Toxic effects (assessed by eye phenotype, longevity and locomotor assays) and levels of the A beta(1-42), A beta(1-40) and A beta(1-38) peptides were examined. Our data reveal that the toxic effect per amount of detected A beta(1-42) peptide was higher in the flies co-expressing A beta PP and BACE1 than in the A beta(1-42)-expressing flies, and that the co-existence of A beta(1-42) and A beta(1-40) in the flies co-expressing A beta PP and BACE1 could be of significant importance to the neurotoxic effect detected in these flies. Thus, the toxicity detected in these two fly models seems to have different modes of action and is highly dependent on how and where the peptide is generated rather than on the actual level of the A beta(1-42) peptide in the flies. This is important knowledge that needs to be taken into consideration when using Drosophila models to investigate disease mechanisms or therapeutic strategies in AD research.

    Place, publisher, year, edition, pages
    COMPANY OF BIOLOGISTS LTD, 2016
    Keywords
    Alzheimers disease; Amyloid-beta (A beta); A beta PP processing; Drosophila melanogaster; Proteotoxicity
    National Category
    Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
    Identifiers
    urn:nbn:se:liu:diva-131685 (URN)10.1242/bio.017194 (DOI)000382304400003 ()27387531 (PubMedID)
    Note

    Funding Agencies|Torsten Soderbergs Stiftelse [M26/11]; Alzheimer Foundation [03-069]; Dementia Foundation; Ahlen Foundation; Gamla Tjanarinnor [2015-00187]

    Available from: 2016-10-03 Created: 2016-09-30 Last updated: 2017-05-16
    2. Beneficial effects of increased lysozyme levels in Alzheimer’s disease modelled in Drosophila melanogaster
    Open this publication in new window or tab >>Beneficial effects of increased lysozyme levels in Alzheimer’s disease modelled in Drosophila melanogaster
    Show others...
    2016 (English)In: The FEBS Journal, ISSN 1742-464X, E-ISSN 1742-4658, Vol. 283, no 19, p. 3508-3522Article in journal (Refereed) Published
    Abstract [en]

    Genetic polymorphisms of immune genes that associate with higher risk to develop Alzheimer’s disease (AD) have led to an increased research interest on the involvement of the immune system in AD pathogenesis. A link between amyloid pathology and immune gene expression was suggested in a genome-wide gene expression study of transgenic amyloid mouse models. In this study, the gene expression of lysozyme, a major player in the innate immune system, was found to be increased in a comparable pattern as the amyloid pathology developed in transgenic mouse models of AD. A similar pattern was seen at protein levels of lysozyme in human AD brain and CSF, but this lysozyme pattern was not seen in a tau transgenic mouse model. Lysozyme was demonstrated to be beneficial for different Drosophila melanogaster models of AD. In flies that expressed Aβ1-42 or AβPP together with BACE1 in the eyes, the rough eye phenotype indicative of toxicity was completely rescued by coexpression of lysozyme. In Drosophila flies bearing the Aβ1-42 variant with the Arctic gene mutation, lysozyme increased the fly survival and decreased locomotor dysfunction dose dependently. An interaction between lysozyme and Aβ1-42 in the Drosophila eye was discovered. We propose that the increased levels of lysozyme, seen in mouse models of AD and in human AD cases, were triggered by Aβ1-42 and caused a beneficial effect by binding of lysozyme to toxic species of Aβ1-42, which prevented these from exerting their toxic effects. These results emphasize the possibility of lysozyme as biomarker and therapeutic target for AD.

    Place, publisher, year, edition, pages
    John Wiley & Sons, 2016
    Keywords
    Alzheimer’s disease, amyloid-β, Drosophila, lysozyme
    National Category
    Genetics Medical Genetics Developmental Biology Bioinformatics and Systems Biology Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
    Identifiers
    urn:nbn:se:liu:diva-131796 (URN)10.1111/febs.13830 (DOI)000386033700001 ()27562772 (PubMedID)
    Available from: 2016-10-07 Created: 2016-10-07 Last updated: 2018-03-20Bibliographically approved
    3. Serum Amyloid P Component Ameliorates Neurological Damage Caused by Expressing a Lysozyme Variant in the Central Nervous System of Drosophila melanogaster
    Open this publication in new window or tab >>Serum Amyloid P Component Ameliorates Neurological Damage Caused by Expressing a Lysozyme Variant in the Central Nervous System of Drosophila melanogaster
    2016 (English)In: PLOS ONE, E-ISSN 1932-6203, Vol. 11, no 7, p. e0159294-Article in journal (Refereed) Published
    Abstract [en]

    Lysozyme amyloidosis is a hereditary disease in which mutations in the gene coding for lysozyme leads to misfolding and consequently accumulation of amyloid material. To improve understanding of the processes involved we expressed human wild type (WT) lysozyme and the disease-associated variant F57I in the central nervous system (CNS) of a Drosophila melanogaster model of lysozyme amyloidosis, with and without co-expression of serum amyloid p component (SAP). SAP is known to be a universal constituent of amyloid deposits and to associate with lysozyme fibrils. There are clear indications that SAP may play an important role in lysozyme amyloidosis, which requires further elucidation. We found that flies expressing the amyloidogenic variant F57I in the CNS have a shorter lifespan than flies expressing WT lysozyme. We also identified apoptotic cells in the brains of F57I flies demonstrating that the flies neurological functions are impaired when F57I is expressed in the nerve cells. However, co-expression of SAP in the CNS prevented cell death and restored the F57I flies lifespan. Thus, SAP has the apparent ability to protect nerve cells from damage caused by F57I. Furthermore, it was found that co-expression of SAP prevented accumulation of insoluble forms of lysozyme in both WT- and F57I-expressing flies. Our findings suggest that the F57I mutation affects the aggregation process of lysozyme resulting in the formation of cytotoxic species and that SAP is able to prevent cell death in the F57I flies by preventing accumulation of toxic F57I structures.

    Place, publisher, year, edition, pages
    PUBLIC LIBRARY SCIENCE, 2016
    National Category
    Developmental Biology
    Identifiers
    urn:nbn:se:liu:diva-131183 (URN)10.1371/journal.pone.0159294 (DOI)000380169300043 ()27428539 (PubMedID)
    Note

    Funding Agencies|Swedish Research Council; Soderberg foundation [M26/11]; Linkoping University Neurobiology Center

    Available from: 2016-09-19 Created: 2016-09-12 Last updated: 2021-06-14
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    Amyloid-β and lysozyme proteotoxicity in Drosophila: Beneficial effects of lysozyme and serum amyloid P component in models of Alzheimer’s disease and lysozyme amyloidosis
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  • 10.
    Bergqvist, Niclas
    et al.
    Linköping University, Department of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Nyman, Elin
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. AstraZeneca RandD, Sweden.
    Cedersund, Gunnar
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Stenkula, Karin G.
    Lund University, Sweden.
    A systems biology analysis connects insulin receptor signaling with glucose transporter translocation in rat adipocytes2017In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 292, no 27, p. 11206-11217Article in journal (Refereed)
    Abstract [en]

    Type 2 diabetes is characterized by insulin resistance, which arises from malfunctions in the intracellular insulin signaling network. Knowledge of the insulin signaling network is fragmented, and because of the complexity of this network, little consensus has emerged for the structure and importance of the different branches of the network. To help overcome this complexity, systems biology mathematical models have been generated for predicting both the activation of the insulin receptor (IR) and the redistribution of glucose transporter 4 (GLUT4) to the plasma membrane. Although the insulin signal transduction between IR and GLUT4 has been thoroughly studied with modeling and time-resolved data in human cells, comparable analyses in cells from commonly used model organisms such as rats and mice are lacking. Here, we combined existing data and models for rat adipocytes with new data collected for the signaling network between IR and GLUT4 to create a model also for their interconnections. To describe all data (amp;gt;140 data points), the model needed three distinct pathways from IR to GLUT4: (i) via protein kinase B (PKB) and Akt substrate of 160 kDa (AS160), (ii) via an AS160-independent pathway from PKB, and (iii) via an additional pathway from IR, e.g. affecting the membrane constitution. The developed combined model could describe data not used for training the model and was used to generate predictions of the relative contributions of the pathways from IR to translocation of GLUT4. The combined model provides a systems-level understanding of insulin signaling in rat adipocytes, which, when combined with corresponding models for human adipocytes, may contribute to model-based drug development for diabetes.

  • 11.
    Berlin, Emmanuel
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Lizano Fallas, Veronica
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Carrasco Del Amor, Ana Maria
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Fresnedo, Olatz
    Univ Basque Country UPV EHU, Spain.
    Cristobal, Susana
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Univ Basque Country UPV EHU, Spain.
    Nonionic Surfactants can Modify the Thermal Stability of Globular and Membrane Proteins Interfering with the Thermal Proteome Profiling Principles to Identify Protein Targets2023In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 95, no 8, p. 4033-4042Article in journal (Refereed)
    Abstract [en]

    The membrane proteins are essential targets for understanding cellular function. The unbiased identification of membrane protein targets is still the bottleneck for a system-level understanding of cellular response to stimuli or perturbations. It has been suggested to enrich the soluble proteome with membrane proteins by introducing nonionic surfactants in the solubilization solution. This strategy aimed to simultaneously identify the globular and membrane protein targets by thermal proteome profiling principles. However, the thermal shift assay would surpass the cloud point temperature from the nonionic surfactants frequently utilized for membrane protein solubilization. It is expected that around the cloud point temperature, the surfactant micelles would suffer structural modifications altering protein solubility. Here, we show that the presence of nonionic surfactants can alter protein thermal stability from a mixed, globular, and membrane proteome. In the presence of surfactant micelles, the changes in protein solubility analyzed after the thermal shift assay was affected by the thermally dependent modification of the micellar size and its interaction with proteins. We demonstrate that the introduction of nonionic surfactants for the solubilization of membrane proteins is not compatible with the principles of target identification by thermal proteome profiling methodologies. Our results lead to exploring thermally independent strategies for membrane protein solubilization to assure confident membrane protein target identification. The proteome-wide thermal shift methods have already shown their capability to elucidate mechanisms of action from pharma, biomedicine, analytical chemistry, or toxicology, and finding strategies, free from surfactants, to identify membrane protein targets would be the next challenge.

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  • 12.
    Birznieks, Ingvars
    et al.
    UNSW Sydney, Australia; Neurosci Res Australia, Australia; Western Sydney Univ, Australia.
    Mcintyre, Sarah
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Neurosci Res Australia, Australia; Western Sydney Univ, Australia.
    Nilsson, Hanna Maria
    Linköping University. Sweden; Neurosci Res Australia, Australia.
    Nagi, Saad
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Western Sydney Univ, Australia.
    Macefield, Vaughan G.
    Neurosci Res Australia, Australia; Western Sydney Univ, Australia; Baker Heart and Diabet Inst, Australia.
    Mahns, David A.
    Western Sydney Univ, Australia.
    Vickery, Richard M.
    UNSW Sydney, Australia; Neurosci Res Australia, Australia.
    Tactile sensory channels over-ruled by frequency decoding system that utilizes spike pattern regardless of receptor type2019In: eLIFE, E-ISSN 2050-084X, Vol. 8, article id e46510Article in journal (Refereed)
    Abstract [en]

    The established view is that vibrotactile stimuli evoke two qualitatively distinctive cutaneous sensations, flutter (frequencies amp;lt; 60 Hz) and vibratory hum (frequencies amp;gt; 60 Hz), subserved by two distinct receptor types (Meissners and Pacinian corpuscle, respectively), which may engage different neural processing pathways or channels and fulfil quite different biological roles. In psychological and physiological literature, those two systems have been labelled as Pacinian and non-Pacinian channels. However, we present evidence that low-frequency spike trains in Pacinian afferents can readily induce a vibratory percept with the same low frequency attributes as sinusoidal stimuli of the same frequency, thus demonstrating a universal frequency decoding system. We achieved this using brief low-amplitude pulsatile mechanical stimuli to selectively activate Pacinian afferents. This indicates that spiking pattern, regardless of receptor type, determines vibrotactile frequency perception. This mechanism may underlie the constancy of vibrotactile frequency perception across different skin regions innervated by distinct afferent types.

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  • 13.
    Bohannon, Briana M.
    et al.
    Univ Miami, FL 33136 USA.
    Jowais, Jessica J.
    Univ Miami, FL 33136 USA.
    Nyberg, Leif
    Linköping University, Department of Biomedical and Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Univ Miami, FL 33136 USA.
    Olivier-Meo, Vanessa
    Univ Miami, FL 33136 USA.
    Corradi, Valentina
    Univ Calgary, Canada.
    Tieleman, D. Peter
    Univ Calgary, Canada.
    Liin, Sara
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences.
    Larsson, H. Peter
    Univ Miami, FL 33136 USA.
    Mechanistic insights into robust cardiac I-Ks potassium channel activation by aromatic polyunsaturated fatty acid analogues2023In: eLIFE, E-ISSN 2050-084X, Vol. 12, article id e85773Article in journal (Refereed)
    Abstract [en]

    Voltage-gated potassium (K-V) channels are important regulators of cellular excitability and control action potential repolarization in the heart and brain. K-V channel mutations lead to disordered cellular excitability. Loss-of-function mutations, for example, result in membrane hyperexcitability, a characteristic of epilepsy and cardiac arrhythmias. Interventions intended to restore K-V channel function have strong therapeutic potential in such disorders. Polyunsaturated fatty acids (PUFAs) and PUFA analogues comprise a class of K-V channel activators with potential applications in the treatment of arrhythmogenic disorders such as long QT syndrome (LQTS). LQTS is caused by a loss-of-function of the cardiac I-Ks channel - a tetrameric potassium channel complex formed by K(V)7.1 and associated KCNE1 protein subunits. We have discovered a set of aromatic PUFA analogues that produce robust activation of the cardiac I-Ks channel, and a unique feature of these PUFA analogues is an aromatic, tyrosine head group. We determine the mechanisms through which tyrosine PUFA analogues exert strong activating effects on the I-Ks channel by generating modified aromatic head groups designed to probe cation-pi interactions, hydrogen bonding, and ionic interactions. We found that tyrosine PUFA analogues do not activate the I-Ks channel through cation-pi interactions, but instead do so through a combination of hydrogen bonding and ionic interactions.

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  • 14.
    Botzanowski, Boris
    et al.
    Aix Marseille Univ, France.
    Donahue, Mary
    Linköping University, Department of Science and Technology, Laboratory of Organic Electronics. Linköping University, Faculty of Science & Engineering.
    Silverå Ejneby, Malin
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. Linköping University, Department of Science and Technology, Laboratory of Organic Electronics. Linköping University, Department of Biomedical and Clinical Sciences, Division of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences.
    Gallina, Alessandro L.
    Ctr Bioelect Med, Sweden; Karolinska Inst, Sweden.
    Ngom, Ibrahima
    Aix Marseille Univ, France.
    Missey, Florian
    Aix Marseille Univ, France.
    Acerbo, Emma
    Aix Marseille Univ, France.
    Byun, Donghak
    Linköping University, Department of Science and Technology, Laboratory of Organic Electronics. Linköping University, Faculty of Science & Engineering.
    Carron, Romain
    Aix Marseille Univ, France.
    Cassara, Antonino M.
    Fdn Res Informat Technol Soc ITIS, Switzerland.
    Neufeld, Esra
    Fdn Res Informat Technol Soc ITIS, Switzerland.
    Jirsa, Viktor
    Aix Marseille Univ, France.
    Olofsson, Peder S.
    Ctr Bioelect Med, Sweden; Karolinska Inst, Sweden; EMUNE AB, Sweden.
    Glowacki, Eric Daniel
    Brno Univ Technol, Czech Republic.
    Williamson, Adam
    Aix Marseille Univ, France; Ctr Bioelect Med, Sweden; Karolinska Inst, Sweden.
    Noninvasive Stimulation of Peripheral Nerves using Temporally-Interfering Electrical Fields2022In: Advanced Healthcare Materials, ISSN 2192-2640, E-ISSN 2192-2659, Vol. 11, no 17, article id 2200075Article in journal (Refereed)
    Abstract [en]

    Electrical stimulation of peripheral nerves is a cornerstone of bioelectronic medicine. Effective ways to accomplish peripheral nerve stimulation (PNS) noninvasively without surgically implanted devices are enabling for fundamental research and clinical translation. Here, it is demonstrated how relatively high-frequency sine-wave carriers (3 kHz) emitted by two pairs of cutaneous electrodes can temporally interfere at deep peripheral nerve targets. The effective stimulation frequency is equal to the offset frequency (0.5 - 4 Hz) between the two carriers. This principle of temporal interference nerve stimulation (TINS) in vivo using the murine sciatic nerve model is validated. Effective actuation is delivered at significantly lower current amplitudes than standard transcutaneous electrical stimulation. Further, how flexible and conformable on-skin multielectrode arrays can facilitate precise alignment of TINS onto a nerve is demonstrated. This method is simple, relying on the repurposing of existing clinically-approved hardware. TINS opens the possibility of precise noninvasive stimulation with depth and efficiency previously impossible with transcutaneous techniques.

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  • 15.
    Brandejsky, Vaclav
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Medical radiation physics.
    Dahlqvist Leinhard, Olof
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Center for Diagnostics, Medical radiation physics.
    Lund, Eva
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Medical radiation physics.
    Lundberg, Peter
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Medical radiation physics. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Phosphorus-31: A table-top method for 3D B1-field amplitude and phase measurements2024In: Biochimica et Biophysica Acta - Biomembranes, ISSN 0005-2736, E-ISSN 1879-2642, Vol. 1866, no 4, article id 184307Article in journal (Refereed)
    Abstract [en]

    A novel method of high -spatial -resolution, 3D B1 -field distribution measurements is presented. The method is independent of the MR -scanner, and it allows for automated acquisitions of complete maps of all magnetic field vector components for both proton and heteronuclear MR coils of arbitrary geometrical shapes. The advantage of the method proposed here, compared with methods based on measurements with an MR -scanner, is that a complete image of both receive and transmit B1 -fields, including the phase of the B1 -field, can be acquired. The B1 field maps obtained in this manner can be used for absolute quantification of metabolites in MRS experiments, as well as for intensity compensations in imaging experiments, both of which are important concepts in biological and medical MR applications. Another use might be in coil development and testing. A comparison with B1 field magnitude maps obtained with an MR -scanner was included to validate the accuracy of the proposed method.

  • 16.
    Brian, Björn
    Linköping University, The Department of Physics, Chemistry and Biology.
    Microarray Technology for Kinetic Analysis of Vesicle Bound Receptor-Ligand Interactions2007Independent thesis Basic level (professional degree), 20 points / 30 hpStudent thesis
    Abstract [en]

    A proof-of-concept for a novel microarray used to study protein-ligand interaction in real-time using label-free detection is presented. Many of todays commercially available instruments lack the ability to immobilize membrane proteins. At the same time, the pharmaceutical industry develops drugs directed towards membrane-bound receptors. The need to study drug-target kinetics and to be able to screen for new medical substances is high. To study the biomolecular interactions in real-time, imaging surface plasmon resonance (iSPR) is used. A patterned sensor surface with hydrophobic barriers assisting in the piezodispensing of NeutrAvidin with complex-bound biotin-ssDNA is created. Histidine-tagged proteins are immobilized at the vesicle surface using divalent nitrilotriacetic acid. The concept of the vesicle immobilization, the protein-binding to vesicles and the protein-ligand interaction is initially studied using a Biacore instrument. The dissociation of the ligand IFNα2 from its receptor ifnar-2 (wt) are in accordance with the literature. In the imaging SPR experiments, it is found that the dissociation of IFNα2 from the ifnar-2 (wt) receptor is slower than expected, probably due to rebinding of the ligand. It is also found that imidazole is needed to avoid vesicle-vesicle interaction. The immobilization of proteins had to be done on-line i.e. when the vesicles were bound to the surface. Depending on the mixture of receptors at the vesicle surface the affinity for the ligand was changed. The results achieved were reproducible.

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  • 17.
    Brodbeck, Christian
    et al.
    McMaster Univ, Canada.
    Das, Proloy
    Stanford Univ, CA USA.
    Gillis, Marlies
    Katholieke Univ Leuven, Belgium.
    Kulasingham, Joshua
    Linköping University, Department of Electrical Engineering, Automatic Control. Linköping University, Faculty of Science & Engineering.
    Bhattasali, Shohini
    Univ Toronto, Canada.
    Gaston, Phoebe
    McMaster Univ, Canada.
    Resnik, Philip
    Univ Maryland, MD USA.
    Simon, Jonathan Z.
    Univ Maryland, MD USA.
    Eelbrain, a Python toolkit for time-continuous analysis with temporal response functions2023In: eLIFE, E-ISSN 2050-084X, Vol. 12, article id e85012Article in journal (Refereed)
    Abstract [en]

    Even though human experience unfolds continuously in time, it is not strictly linear; instead, it entails cascading processes building hierarchical cognitive structures. For instance, during speech perception, humans transform a continuously varying acoustic signal into phonemes, words, and meaning, and these levels all have distinct but interdependent temporal structures. Time-lagged regression using temporal response functions (TRFs) has recently emerged as a promising tool for disentangling electrophysiological brain responses related to such complex models of perception. Here, we introduce the Eelbrain Python toolkit, which makes this kind of analysis easy and accessible. We demonstrate its use, using continuous speech as a sample paradigm, with a freely available EEG dataset of audiobook listening. A companion GitHub repository provides the complete source code for the analysis, from raw data to group-level statistics. More generally, we advocate a hypothesis-driven approach in which the experimenter specifies a hierarchy of time-continuous representations that are hypothesized to have contributed to brain responses, and uses those as predictor variables for the electrophysiological signal. This is analogous to a multiple regression problem, but with the addition of a time dimension. TRF analysis decomposes the brain signal into distinct responses associated with the different predictor variables by estimating a multivariate TRF (mTRF), quantifying the influence of each predictor on brain responses as a function of time(-lags). This allows asking two questions about the predictor variables: (1) Is there a significant neural representation corresponding to this predictor variable? And if so, (2) what are the temporal characteristics of the neural response associated with it? Thus, different predictor variables can be systematically combined and evaluated to jointly model neural processing at multiple hierarchical levels. We discuss applications of this approach, including the potential for linking algorithmic/representational theories at different cognitive levels to brain responses through computational models with appropriate linking hypotheses.

  • 18.
    Burtscher, Bernhard
    et al.
    Linköping University, Department of Science and Technology, Laboratory of Organic Electronics. Linköping University, Faculty of Science & Engineering.
    Urbina, Pamela Allison Manco
    Univ Modena & Reggio Emilia, Italy.
    Diacci, Chiara
    Linköping University, Department of Science and Technology, Laboratory of Organic Electronics. Linköping University, Faculty of Science & Engineering.
    Borghi, Simone
    Univ Modena & Reggio Emilia, Italy.
    Pinti, Marcello
    Univ Modena & Reggio Emilia, Italy.
    Cossarizza, Andrea
    Univ Modena & Reggio Emilia, Italy.
    Salvarani, Carlo
    Univ Modena & Reggio Emilia, Italy.
    Berggren, Magnus
    Linköping University, Department of Science and Technology, Laboratory of Organic Electronics. Linköping University, Faculty of Science & Engineering.
    Biscarini, Fabio
    Univ Modena & Reggio Emilia, Italy; Ist Italiano Tecnol, Italy.
    Simon, Daniel
    Linköping University, Department of Science and Technology, Laboratory of Organic Electronics. Linköping University, Faculty of Science & Engineering.
    Bortolotti, Carlo A.
    Univ Modena & Reggio Emilia, Italy.
    Sensing Inflammation Biomarkers with Electrolyte-Gated Organic Electronic Transistors2021In: Advanced Healthcare Materials, ISSN 2192-2640, E-ISSN 2192-2659, Vol. 10, no 20, article id 2100955Article, review/survey (Refereed)
    Abstract [en]

    An overview of cytokine biosensing is provided, with a focus on the opportunities provided by organic electronic platforms for monitoring these inflammation biomarkers which manifest at ultralow concentration levels in physiopathological conditions. Specifically, two of the fields state-of-the-art technologies-organic electrochemical transistors (OECTs) and electrolyte gated organic field effect transistors (EGOFETs)-and their use in sensing cytokines and other proteins associated with inflammation are a particular focus. The overview will include an introduction to current clinical and "gold standard" quantification techniques and their limitations in terms of cost, time, and required infrastructure. A critical review of recent progress with OECT- and EGOFET-based protein biosensors is presented, alongside a discussion onthe future of these technologies in the years and decades ahead. This is especially timely as the world grapples with limited healthcare diagnostics during the Coronavirus disease (COVID-19)pandemic where one of the worst-case scenarios for patients is the "cytokine storm." Clearly, low-cost point-of-care technologies provided by OECTs and EGOFETs can ease the global burden on healthcare systems and support professionals by providing unprecedented wealth of data that can help to monitor disease progression in real time.

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  • 19. Order onlineBuy this publication >>
    del Río, Lía Fernández
    Linköping University, Department of Physics, Chemistry and Biology, Applied Optics. Linköping University, Faculty of Science & Engineering.
    Optical and Structural Characterization of Natural Nanostructures2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The spectacular biodiversity of our planet is the result of millions of years of evolution. Over this time animals and plants have evolved and adapted to different environments, developing specific behavioral and physical adaptations to increase their chances of survival. During the last centuries human's curiosity has pushed us to study and understand the phenomena and mechanisms of the nature that surrounds us. This understanding has even led to the fields of biomimetics where we seek solutions to human challenges by emulating nature.

    Scarab beetles (from the insect family Scarabaeidae) have fascinated humans for centuries due to the brilliant metallic shine of their chitin-rich exoskeletons and more recently for their ability to polarize reflected light. This doctoral thesis focuses on the optical characterization of the polarized reflected light from beetles in the Chrysina genus, although beetles from other genera also have been investigated. All the Chrysina beetles studied here share one characteristic, they all reflect left-handed near-circular polarized light. In some cases we also detect right-handed polarized light.

    We have observed two different main behaviors among the studied Chrysina beetles. Those which are green-colored scatter the reflected polarized light, whereas those with metallic appearance are broadband specular reflectors. We present a detailed analysis of the optical properties with Mueller-matrix spectroscopic ellipsometry combined with optical- and electron-microscopy studies of the exoskeletons. This allow us to create a model that reproduces the optical properties of these structures. The model consists of a chiral (helicoidal) multilayer structure with a gradual change of the pitch and a constant rotation of the optic axis of the layers.

    Beetles are not alone to have polarizing structures in nature and it is known that many birds and insects have the ability to detect linearly polarized light. This raises the question of whether the polarization properties of the beetles are the direct or indirect results of evolution or just pure coincidence. In order to get a better understanding of the possible reasons of this particular ability, we present a simulation study of different possible scenarios in nature where incoming light could be polarized or unpolarized, and where we consider detectors (eyes) sensitive to different states of polarized light. If the beetles are able to use this characteristic for camouflage, to confuse predators or for intraspecific communication is,

    however, still unknown and requires further investigation.

    My research results provide deeper understanding of the properties of light reflected on the beetle's exoskeleton and the nanostructures responsible for the polarization of the reflected light. The developed model could be used as bioinspiration for the fabrication of novel nano-optical devices. My results can also complement biological behavioral experiments aiming to understand the purposes of this specific optical characteristics in nature.

    List of papers
    1. Polarizing properties and structure of the cuticle of scarab beetles from the Chrysina genus
    Open this publication in new window or tab >>Polarizing properties and structure of the cuticle of scarab beetles from the Chrysina genus
    2016 (English)In: PHYSICAL REVIEW E, ISSN 2470-0045, Vol. 94, no 1, p. 012409-Article in journal (Refereed) Published
    Abstract [en]

    The optical properties of several scarab beetles have been previously studied but few attempts have been made to compare beetles in the same genus. To determine whether there is any relation between specimens of the same genus, we have studied and classified seven species from the Chrysina genus. The polarization properties were analyzed with Mueller-matrix spectroscopic ellipsometry and the structural characteristics with optical microscopy and scanning electron microscopy. Most of the Chrysina beetles are green colored or have a metallic look (gold or silver). The results show that the green-colored beetles polarize reflected light mainly at off-specular angles. The gold-colored beetles polarize light left-handed near circular at specular reflection. The structure of the exoskeleton is a stack of layers that form a cusplike structure in the green beetles whereas the layers are parallel to the surface in the case of the gold-colored beetles. The beetle C. gloriosa is green with gold-colored stripes along the elytras and exhibits both types of effects. The results indicate that Chrysina beetles can be classified according to these two major polarization properties.

    Place, publisher, year, edition, pages
    AMER PHYSICAL SOC, 2016
    National Category
    Mathematical Analysis
    Identifiers
    urn:nbn:se:liu:diva-130835 (URN)10.1103/PhysRevE.94.012409 (DOI)000380116500010 ()
    External cooperation:
    Note

    Funding Agencies|Knut and Alice Wallenberg foundation; Swedish Research Council; Centre in Nano Science and Nano Technology (CeNano) at Linkoping University

    Available from: 2016-08-26 Created: 2016-08-26 Last updated: 2016-11-16
    2. Polarizing properties and structural characteristics of the cuticle of the scarab Beetle Chrysina gloriosa
    Open this publication in new window or tab >>Polarizing properties and structural characteristics of the cuticle of the scarab Beetle Chrysina gloriosa
    2014 (English)In: Thin Solid Films, ISSN 0040-6090, E-ISSN 1879-2731, Vol. 571, no 3, p. 410-415Article in journal (Refereed) Published
    Abstract [en]

    The scarab beetle Chrysina gloriosa is green with gold-colored stripes along its elytras. The properties of light reflected on these areas are investigated using Mueller-matrix spectroscopic ellipsometry. Both areas reflect light with high degree of left-handed polarization but this effect occurs for specular reflection for the gold-colored areas and for off-specular angles for the green areas. The colors and polarization phenomena originate from reflection of light in the cuticle and a structural analysis is presented to facilitate understanding of the different behaviors of these two areas. Scanning electron microscopy (SEM) images of the cross section of beetle cuticles show a multilayered structure. On the gold-colored areas the layers are parallel to the surface whereas on the green-colored areas they form cusp-like structures. Optical microscopy images show a rather flat surface in the gold-colored areas compared to the green-colored areas which display a net of polygonal cells with star-shaped cavities in the center. Each of the polygons corresponds to one of the cusps observed in the SEM images. Atomic force microscopy images of the star-shaped cavities are also provided. The roughness of the surface and the cusp-like structure of the green-colored areas are considered to cause scattering on this area.

    Place, publisher, year, edition, pages
    Elsevier, 2014
    Keywords
    Scarab beetle; Near-circular polarization; Mueller-matrix spectroscopic ellipsometry
    National Category
    Atom and Molecular Physics and Optics
    Identifiers
    urn:nbn:se:liu:diva-112885 (URN)10.1016/j.tsf.2013.11.149 (DOI)000346055200013 ()
    Conference
    ICSE-VI International Conference on Spectroscopic Ellipsometry May 2013
    Funder
    Swedish Research CouncilKnut and Alice Wallenberg Foundation
    Available from: 2014-12-18 Created: 2014-12-18 Last updated: 2017-12-05Bibliographically approved
    3. Polarization of light reflected from Chrysina gloriosa under various illuminations
    Open this publication in new window or tab >>Polarization of light reflected from Chrysina gloriosa under various illuminations
    2014 (English)In: Materials Today: Proceedings, Elsevier Ltd , 2014, Vol. 1, p. 172-176Conference paper, Published paper (Refereed)
    Abstract [en]

    When illuminated with unpolarized light, the scarab beetle Chrysina gloriosa, reflects left-handed near-circularly polarized light for a broad range of angles of incidence and wavelengths in the visible. It is, however, known that light scattered from the sky, reflected on water or transmitted through leaves often is linearly polarized. In this study we have analysed the polarization of light reflected on this beetle when illuminated with different polarization states of light. We have also analysed how the response would be with a polarization-sensitive detector. The reflected irradiance is shown to be highest when the incident light is s-polarized or left-handed polarized and the detector is unpolarized (or vice versa). In the case in which both, the source and the detector, are polarized, the irradiance is highest when both are s-polarized. On the contrary the visibility is low when the source is s-polarized and the detector is p-polarized.

    Place, publisher, year, edition, pages
    Elsevier Ltd, 2014
    Series
    Materials Today: Proceedings, ISSN 2214-7853
    Keywords
    Mueller-matrix spectroscopic ellipsometry; Near-circular polarization; Scarab beetle
    National Category
    Physical Sciences
    Identifiers
    urn:nbn:se:liu:diva-116444 (URN)10.1016/j.matpr.2014.09.020 (DOI)2-s2.0-84923048023 (Scopus ID)
    Conference
    Living Light: Uniting biology and photonics - A memorial meeting in honour of Prof Jean-Pol Vigneron
    Available from: 2015-03-27 Created: 2015-03-26 Last updated: 2016-11-16
    4. Comparison and analysis of Mueller-matrix spectra from exoskeletons of blue, green and red Cetonia aurata
    Open this publication in new window or tab >>Comparison and analysis of Mueller-matrix spectra from exoskeletons of blue, green and red Cetonia aurata
    2014 (English)In: Thin Solid Films, ISSN 0040-6090, E-ISSN 1879-2731, Vol. 571, p. 739-743Article in journal (Refereed) Published
    Abstract [en]

    The exoskeleton, also called the cuticle, of specimens of the scarab beetle Cetonia aurata is a narrow-band reflector which exhibits metallic shine. Most specimens of C. aurata have a reflectance maximum in the green part of the spectrum but variations from blue–green to red–green are also found. A few specimens are also more distinct blue or red. Furthermore, the reflected light is highly polarized and at near-normal incidence near-circular left-handed polarization is observed. The polarization and color phenomena are caused by a nanostructure in the cuticle. This nanostructure can be modeled as a multilayered twisted biaxial layer from which reflection properties can be calculated. Specifically we calculate the cuticle Mueller matrix which then is fitted to Mueller matrices determined by dual-rotating compensator ellipsometry in the spectral range 400–800 nm at multiple angles of incidence. This non-linear regression analysis provides structural parameters like pitch of the chiral structure as well as layer refractive index data for the different layers in the cuticle. The objective here is to compare spectra measured on C. aurata with different colors and develop a generic structural model. Generally the degree of polarization is large in the spectral region corresponding to the color of the cuticle which for the blue specimen is 400–600 nm whereas for the red specimen it is 530–730 nm. In these spectral ranges, the Mueller-matrix element m41 is non-zero and negative, in particular for small angles of incidence, implicating that the reflected light becomes near-circularly polarizedwith an ellipticity angle in the range 20°–45°.

    Place, publisher, year, edition, pages
    Elsevier, 2014
    Keywords
    Mueller-matrix ellipsometry; Scarab beetles; Chiral structures; Circular polarization; Natural photonic structures
    National Category
    Condensed Matter Physics
    Identifiers
    urn:nbn:se:liu:diva-112685 (URN)10.1016/j.tsf.2014.02.012 (DOI)000346055200076 ()
    Conference
    6th International Conference on Spectroscopic Ellipsometry (ICSE-VI), May 26–31, 2013, Kyoto, Japan
    Funder
    Knut and Alice Wallenberg FoundationSwedish Research Council
    Available from: 2014-12-08 Created: 2014-12-08 Last updated: 2017-12-05Bibliographically approved
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    Optical and Structural Characterization of Natural Nanostructures
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  • 20.
    Du, Zhixue
    et al.
    Royal Inst Technol KTH, Sweden.
    Piguet, Joachim
    Royal Inst Technol KTH, Sweden.
    Baryshnikov, Glib
    Linköping University, Department of Science and Technology, Laboratory of Organic Electronics. Linköping University, Faculty of Science & Engineering.
    Tornmalm, Johan
    Royal Inst Technol KTH, Sweden.
    Demirbay, Baris
    Royal Inst Technol KTH, Sweden.
    Ågren, Hans
    Uppsala Univ, Sweden.
    Widengren, Jerker
    Royal Inst Technol KTH, Sweden.
    Imaging Fluorescence Blinking of a Mitochondrial Localization Probe: Cellular Localization Probes Turned into Multifunctional Sensors2022In: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 126, no 16, p. 3048-3058Article in journal (Refereed)
    Abstract [en]

    Mitochondrial membranes and their microenviron-ments directly influence and reflect cellular metabolic states but aredifficult to probe on site in live cells. Here, we demonstrate astrategy, showing how the widely used mitochondrial membranelocalizationfluorophore 10-nonyl acridine orange (NAO) can betransformed into a multifunctional probe of membrane micro-environments by monitoring its blinking kinetics. By transient state(TRAST) studies of NAO in small unilamellar vesicles (SUVs),together with computational simulations, we found that NAOexhibits prominent reversible singlet-triplet state transitions andcan act as a light-induced Lewis acid forming a red-emissivedoublet radical. The resulting blinking kinetics are highlyenvironment-sensitive, specifically reflecting local membrane oxy-gen concentrations, redox conditions, membrane charge,fluidity, and lipid compositions. Here, not only cardiolipin concentrationbut also the cardiolipin acyl chain composition was found to strongly influence the NAO blinking kinetics. The blinking kinetics alsoreflect hydroxyl ion-dependent transitions to and from thefluorophore doublet radical, closely coupled to the proton-transfer eventsin the membranes, local pH, and two- and three-dimensional buffering properties on and above the membranes. Following the SUVstudies, we show by TRAST imaging that thefluorescence blinking properties of NAO can be imaged in live cells in a spatiallyresolved manner. Generally, the demonstrated blinking imaging strategy can transform existingfluorophore markers intomultiparametric sensors reflecting conditions of large biological relevance, which are difficult to retrieve by other means. This opensadditional possibilities for fundamental membrane studies in lipid vesicles and live cells

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  • 21. Order onlineBuy this publication >>
    Eskilson, Olof
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Multifunctional Nanocellulose Composite Materials2023Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Nanoparticles (NPs) are particles with more than one dimension between 1 and 100 nm. Because of their small size, they typically display different physical and chemical properties than the corresponding bulk materials. NPs have been used in many different applications, such as in electronics, optics, catalysis, and in biomedicine. Due to their colloidal nature, NPs are often immobilized on a solid substrate, such as glass or polymer-based materials, including biopolymers. Nanocellulose is a biopolymerbased nanomaterial that can be obtained from plants or bacterial biofilms. They can be processed into thin and highly hydrated films with high mechanical strength and can serve as a versatile substrate for NPs. Bacterial cellulose (BC) is also an interesting material for generating wound dressings. The combination of NPs and BC results in soft and flexible nanocomposites (BC-NPs) that can demonstrate novel properties and improve the functionality of wound dressings. 

    BC-NP nanocomposites have previously been obtained by impregnating BC with the reactants needed for synthesis of the NPs and allowing the reaction to proceed in situ, inside and on the surface of the BC. This strategy limits the possibilities to control NP geometry and NP concentration and make synthesis of nanocomposites with more sophisticated compositions very challenging. In addition, the synthesis conditions used can potentially have negative effects on the properties of BC. 

    The work presented in this thesis shows the possibility to produce well-defined, tunable BC-NP nanocomposites using self-assembly under very benign conditions that enable functionalization of BC with a wide range of different types of NPs. In addition to exploring the self-assembly process and the physical properties of these new BC-NP composites, several different applications were investigated. The functionalization of BC with gold nanoparticles (AuNPs) of different sizes and geometries was demonstrated. The resulting materials were used for development of a new sensor transduction technology, exploiting the optical response upon mechanical compression to detect biomolecules. BC-AuNP nanocomposites were also developed for monitoring of protease activity of wound pathogens, for catalysis, and for fabrication of ultra-black materials with unique absorption and scattering profiles of light in the visible and near infrared spectral range. In addition, the self-assembly process could be adopted for generating BC-mesoporous silica nanoparticles (MSNs) nanocomposite wound dressings. The resulting high surface area materials could be used as carriers for pH sensitive dyes. The pH-responsive BC-MSNs demonstrated adequate biocompatibility and allowed for monitoring of wound pH and for assessment of wound status. 

    The strategies for functionalization of BC with inorganic NPs that was developed and explored in this thesis are highly versatile and allow for fabrication of a wide range of multifunctional nanocomposite materials. 

    List of papers
    1. Self-Assembly of Mechanoplasmonic Bacterial Cellulose-Metal Nanoparticle Composites
    Open this publication in new window or tab >>Self-Assembly of Mechanoplasmonic Bacterial Cellulose-Metal Nanoparticle Composites
    Show others...
    2020 (English)In: Advanced Functional Materials, ISSN 1616-301X, E-ISSN 1616-3028, Vol. 30, no 40, article id 2004766Article in journal (Refereed) Published
    Abstract [en]

    Nanocomposites of metal nanoparticles (NPs) and bacterial nanocellulose (BC) enable fabrication of soft and biocompatible materials for optical, catalytic, electronic, and biomedical applications. Current BC-NP nanocomposites are typically prepared by in situ synthesis of the NPs or electrostatic adsorption of surface functionalized NPs, which limits possibilities to control and tune NP size, shape, concentration, and surface chemistry and influences the properties and performance of the materials. Here a self-assembly strategy is described for fabrication of complex and well-defined BC-NP composites using colloidal gold and silver NPs of different sizes, shapes, and concentrations. The self-assembly process results in nanocomposites with distinct biophysical and optical properties. In addition to antibacterial materials and materials with excellent senor performance, materials with unique mechanoplasmonic properties are developed. The homogenous incorporation of plasmonic gold NPs in the BC enables extensive modulation of the optical properties by mechanical stimuli. Compression gives rise to near-field coupling between adsorbed NPs, resulting in tunable spectral variations and enhanced broadband absorption that amplify both nonlinear optical and thermoplasmonic effects and enables novel biosensing strategies.

    Place, publisher, year, edition, pages
    WILEY-V C H VERLAG GMBH, 2020
    Keywords
    antimicrobials; bacterial cellulose; gold nanoparticles; nanocomposite; sensors
    National Category
    Materials Chemistry
    Identifiers
    urn:nbn:se:liu:diva-168770 (URN)10.1002/adfm.202004766 (DOI)000557380700001 ()
    Note

    Funding Agencies|Swedish Foundation for Strategic Research (SFF)Swedish Foundation for Strategic Research [FFL15-0026, RMX18-0039]; Swedish Government Strategic Research Area in Materials Science on Functional Materials at Linkoping University [2009-00971]; VinnovaVinnova [2016-05156]; Knut and Alice Wallenberg FoundationKnut & Alice Wallenberg Foundation [KAW 2016.0231]; Swedish Research CouncilSwedish Research Council [2017-05178, 2015-05002]; Spanish Ministerio de Ciencia, Innovacion y Universidades (MICINN) [MAT2016-77391-R]; Severo Ochoa Centres of Excellence programme - Spanish Research Agency (AEI) [SEV-2017-0706]

    Available from: 2020-08-31 Created: 2020-08-31 Last updated: 2023-05-24
    2. Nanocellulose composite wound dressings for real-time pH wound monitoring
    Open this publication in new window or tab >>Nanocellulose composite wound dressings for real-time pH wound monitoring
    Show others...
    2023 (English)In: Materials Today Bio, ISSN 2590-0064, Vol. 19, article id 100574Article in journal (Refereed) Published
    Abstract [en]

    The skin is the largest organ of the human body. Wounds disrupt the functions of the skin and can have catastrophic consequences for an individual resulting in significant morbidity and mortality. Wound infections are common and can substantially delay healing and can result in non-healing wounds and sepsis. Early diagnosis and treatment of infection reduce risk of complications and support wound healing. Methods for monitoring of wound pH can facilitate early detection of infection. Here we show a novel strategy for integrating pH sensing capabilities in state-of-the-art hydrogel-based wound dressings fabricated from bacterial nanocellulose (BC). A high surface area material was developed by self-assembly of mesoporous silica nanoparticles (MSNs) in BC. By encapsulating a pH-responsive dye in the MSNs, wound dressings for continuous pH sensing with spatiotemporal resolution were developed. The pH responsive BC-based nanocomposites demonstrated excellent wound dressing properties, with respect to conformability, mechanical properties, and water vapor transmission rate. In addition to facilitating rapid colorimetric assessment of wound pH, this strategy for generating functional BC-MSN nanocomposites can be further be adapted for encapsulation and release of bioactive compounds for treatment of hard-to-heal wounds, enabling development of novel wound care materials.

    Place, publisher, year, edition, pages
    Elsevier, 2023
    Keywords
    Bacterial nanocellulose, Wound dressing, pH sensor, Infection, Mesoporous silica nanoparticles
    National Category
    Biomaterials Science
    Identifiers
    urn:nbn:se:liu:diva-192408 (URN)10.1016/j.mtbio.2023.100574 (DOI)000944392500001 ()36852226 (PubMedID)
    Note

    Funding agencies: This work was supported by the Swedish Foundation for Strategic Research (SFF) grant no. FFL15-0026 and framework grant RMX18-0039 (HEALiX), the Swedish Government Strategic Research Area in Materials Science on Functional Materials at Linköping University (Faculty Grant SFO-Mat-LiU no. 2009–00971), the competence center FunMat-II that is financially supported by Vinnova (grant no. 2016-05156), the Knut and Alice Wallenberg Foundation (grant no. KAW 2016.0231), the Swedish Research Council (VR) (grant no. 2021-04427) and Swedish strategic research program Bio4Energy. Illustrations were created with BioRender.com. We thank S2Medical AB, Linköping, Sweden, for providing BC.

    Available from: 2023-03-15 Created: 2023-03-15 Last updated: 2024-05-01Bibliographically approved
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  • 22.
    Feuz, Laurent
    et al.
    Department of Applied Physics, Chalmers University of Technology, SE-41296 Gothenburg, Sweden.
    Jonsson, Magnus P.
    Department of Applied Physics, Chalmers University of Technology, SE-41296 Gothenburg, Sweden.
    Hook, Fredrik
    Department of Applied Physics, Chalmers University of Technology, SE-41296 Gothenburg, Sweden.
    Material-Selective Surface Chemistry for Nanoplasmonic Sensors: Optimizing Sensitivity and Controlling Binding to Local Hot Spots2012In: Nano letters (Print), ISSN 1530-6984, E-ISSN 1530-6992, Vol. 12, no 2, p. 873-879Article in journal (Refereed)
    Abstract [en]

    Optical sensors utilizing the principle of localized surface plasmon resonance (LSPR) offer the advantage of a simple label-free mode of operation, but the sensitivity is typically limited to a very thin region close to the surface. In bioanalytical sensing applications, this can be a significant drawback, in particular since the surface needs to be coated with a recognition layer in order to ensure specific detection of target molecules. We show that the signal upon protein binding decreases dramatically with increasing thickness of the recognition layer, highlighting the need for thin high quality recognition layers compatible with LSPR sensors. The effect is particularly strong for structures that provide local hot spots with highly confined fields, such as in the gap between pairs of gold disks. While our results show a significant improvement in sensor response for pairs over single gold disks upon binding directly to the gold surface, disk pairs did not provide larger signal upon binding of proteins to a recognition layer (already for around 3 nm thin layers) located on the gold. Local plasmonic hot spots are however shown advantageous in combination with directed binding to the hot spots. This was demonstrated using a structure consisting of three surface materials (gold, titanium dioxide, and silicon dioxide) and a new protocol for material-selective surface chemistry of these three materials, which allows for controlled binding only in the gap between pairs of disks. Such a design increased the signal obtained per bound molecule by a factor of around four compared to binding to single disks.

  • 23.
    Feuz, Laurent
    et al.
    Department of Applied Physics, Chalmers University of Technology, SE-41296 Gothenburg, Sweden.
    Jonsson, Peter
    Department of Applied Physics, Chalmers University of Technology, SE-41296 Gothenburg, Sweden.
    Jonsson, Magnus P.
    Department of Applied Physics, Chalmers University of Technology, SE-41296 Gothenburg, Sweden.
    Hook, Fredrik
    Department of Applied Physics, Chalmers University of Technology, SE-41296 Gothenburg, Sweden.
    Improving the Limit of Detection of Nanoscale Sensors by Directed Binding to High-Sensitivity Areas2010In: ACS Nano, ISSN 1936-0851, E-ISSN 1936-086X, Vol. 4, no 4, p. 2167-2177Article in journal (Refereed)
    Abstract [en]

    The revelation of protein protein-interactions is one of the main preoccupations in the field of proteomics. Nanoplasmonics has emerged as an attractive surface-based technique because of its ability to sense protein binding under physiological conditions in a label-free manner. Here, we use short-range ordered holes with a diameter of similar to 150 nm and a depth of similar to 50 nm as a nanoplasmonic template. A similar to 40 nm high cylindrical region of Au is exposed on the walls of the holes only, while the rest of the surface consists of TiO(2). Since the sensitivity is confined to the nanometric holes, the use of two different materials for the sensor substrate offers the opportunity to selectively bind proteins to the most sensitive Au regions on the sensor surface. This was realized by applying material-selective poly(ethylene glycol)-based surface chemistry, restricting NeutrAvidin binding to surface-immobilized biotin on the Au areas only. We show that under mass-transport limited conditions (low nM bulk concentrations), the initial time-resolved response of uptake could be increased by a factor of almost 20 compared with the case where proteins were allowed to bind on the entire sensor surface and stress the generic relevance of this concept for nanoscale sensors. In the scope of further optimizing the limit of detection (LOD) of the sensor structure, we present finite-element (FE) simulations to unravel spatially resolved binding rates. These revealed that the binding rates in the holes occur in a highly inhomogeneous manner with highest binding rates observed at the upper rim of the holes and the lowest rates observed at the bottom of the holes. By assuming a plasmonic field distribution with enhanced sensitivity at the Au-TiO(2)interface, the FE simulations reproduced the experimental findings qualitatively.

  • 24.
    Firouznia, Marjan
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Henningsson, Markus
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Carlhäll, Carljohan
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    FK-means: automatic atrial fibrosis segmentation using fractal-guided K-means clustering with Voronoi-clipping feature extraction of anatomical structures2023In: Interface Focus, ISSN 2042-8898, E-ISSN 2042-8901, Vol. 13, no 6, article id 20230033Article in journal (Refereed)
    Abstract [en]

    Assessment of left atrial (LA) fibrosis from late gadolinium enhancement (LGE) magnetic resonance imaging (MRI) adds to the management of patients with atrial fibrillation. However, accurate assessment of fibrosis in the LA wall remains challenging. Excluding anatomical structures in the LA proximity using clipping techniques can reduce misclassification of LA fibrosis. A novel FK-means approach for combined automatic clipping and automatic fibrosis segmentation was developed. This approach combines a feature-based Voronoi diagram with a hierarchical 3D K-means fractal-based method. The proposed automatic Voronoi clipping method was applied on LGE-MRI data and achieved a Dice score of 0.75, similar to the score obtained by a deep learning method (3D UNet) for clipping (0.74). The automatic fibrosis segmentation method, which uses the Voronoi clipping method, achieved a Dice score of 0.76. This outperformed a 3D UNet method for clipping and fibrosis classification, which had a Dice score of 0.69. Moreover, the proposed automatic fibrosis segmentation method achieved a Dice score of 0.90, using manual clipping of anatomical structures. The findings suggest that the automatic FK-means analysis approach enables reliable LA fibrosis segmentation and that clipping of anatomical structures in the atrial proximity can add to the assessment of atrial fibrosis.

  • 25.
    Frampton, Damon
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences.
    Choudhury, Koushik
    KTH Royal Inst Technol, Sweden.
    Nikesjö, Johan
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences.
    Delemotte, Lucie
    KTH Royal Inst Technol, Sweden.
    Liin, Sara
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences.
    Subtype-specific responses of hKv7.4 and hKv7.5 channels to polyunsaturated fatty acids reveal an unconventional modulatory site and mechanism2022In: eLIFE, E-ISSN 2050-084X, Vol. 11, article id e77672Article in journal (Refereed)
    Abstract [en]

    The K(V)7.4 and K(V)7.5 subtypes of voltage -gated potassium channels play a role in important physiological processes such as sound amplification in the cochlea and adjusting vascular smooth muscle tone. Therefore, the mechanisms that regulate K(V)7.4 and K(V)7.5 channel function are of interest. Here, we study the effect of polyunsaturated fatty acids (PUFAs) on human K(V)7.4 and KV7.5 channels expressed in Xenopus oocytes. We report that PUFAs facilitate activation of hK(V)7.5 by shifting the V50 of the conductance versus voltage (G(V)) curve toward more negative voltages. This response depends on the head group charge, as an uncharged PUFA analogue has no effect and a positively charged PUFA analogue induces positive V-50 shifts. In contrast, PUFAs inhibit activation of hK(V)7.4 by shifting V-50 toward more positive voltages. No effect on V-50 of hK(V)7.4 is observed by an uncharged or a positively charged PUFA analogue. Thus, the hK(V)7.5 channels response to PUFAs is analogous to the one previously observed in hK(V)7.1-7.3 channels, whereas the hK(V)7.4 channel response is opposite, revealing subtype-specific responses to PUFAs. We identify a unique inner PUFA interaction site in the voltage-sensing domain of hKV7.4 underlying the PUFA response, revealing an unconventional mechanism of modulation of hK(V)7.4 by PUFAs.

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  • 26.
    Franco-Gonzalez, Juan F.
    et al.
    BIOPHYM, IEM, CSIC, Madrid, Spain.
    Cruz, Victor
    BIOPHYM, IEM, CSIC, Madrid, Spain.
    Ramos, Javier
    BIOPHYM, IEM, CSIC, Madrid, Spain.
    Martinez-Salazar, Javier
    BIOPHYM, IEM, CSIC, Madrid, Spain.
    Protein-Protein and Protein-Membrane Interactions Regarding the Erbb2/Trastuzumab-Fab Complexes. A Coarse-Grained Molecular Dynamics Description2014In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 106, no 2, p. 666-667Article in journal (Refereed)
    Abstract [en]

    ErbB2 is a member of epidermal growth factor receptor (EGFR) family and is overexpressed in many cancers. Specifically, Trastuzumab, which is a monoclonal antibody, is used against ErbB2, but its action mechanism is still unknown. ErbB2 can exist as both monomers and Homodimers, suggesting that Trastuzumab mechanims may be subtle. On the other hand, the membrane plays a role in the action mechanism of Trastuzumab but generates difficulties for structural studies. Coarse-Grained Molecular Dynamics has been used to study the influence of the Trastuzumab on the protein-protein and protein-membrane interactions of the full ErbB2 receptor. Our simulations start from conformations which both extracelullar and intracelullar domains are extended. The results show in both monomers and homodimers systems a folded conformation on the membrane: several experimental results, mainly obtained on ErbB1 support them. The protein-protein interaction on transmembrane and juxtamembrane domains are disrupted on the dimer and disordered on the monomer by the Trastuzumab effect, therefore, the dimerization-driven activation are unfavourable. We present a detailed description of the type of interactions governing the homodimerization and antobody complexation phenomena and the role that the membrane plays on that.

  • 27.
    Franco-Gonzalez, Juan Felipe
    et al.
    Macromolecular Physics Department, Instituto de Estructura de la Materia, CSIC, Madrid, Spain.
    Cruz, Victor L
    Macromolecular Physics Department, Instituto de Estructura de la Materia, CSIC, Madrid, Spain.
    Ramos, Javier
    Macromolecular Physics Department, Instituto de Estructura de la Materia, CSIC, Madrid, Spain.
    Martínez-Salazar, Javier
    Macromolecular Physics Department, Instituto de Estructura de la Materia, CSIC, Madrid, Spain.
    Conformational flexibility of the ErbB2 ectodomain and trastuzumab antibody complex as revealed by molecular dynamics and principal component analysis.2013In: Journal of Molecular Modeling, ISSN 1610-2940, E-ISSN 0948-5023, Vol. 19, no 3, p. 1227-1236Article in journal (Refereed)
    Abstract [en]

    Human epidermal growth factor receptor 2 (ErbB2) is a transmembrane oncoprotein that is over expressed in breast cancer. A successful therapeutic treatment is a monoclonal antibody called trastuzumab which interacts with the ErbB2 extracellular domain (ErbB2-ECD). A better understanding of the detailed structure of the receptor-antibody interaction is indeed of prime interest for the design of more effective anticancer therapies. In order to discuss the flexibility of the complex ErbB2-ECD/trastuzumab, we present, in this study, a multi-nanosecond molecular dynamics simulation (MD) together with an analysis of fluctuations, through a principal component analysis (PCA) of this system. Previous to this step and in order to validate the simulations, we have performed a detailed analysis of the variable antibody domain interactions with the extracellular domain IV of ErbB2. This structure has been statically elucidated by x-ray studies. Indeed, the simulation results are in excellent agreement with the available experimental information during the full trajectory. The PCA shows eigenvector fluctuations resulting in a hinge motion in which domain II and C(H) domains approach each other. This move is likely stabilized by the formation of H-bonds and salt bridge interactions between residues of the dimerization arm in the domain II and trastuzumab residues located in the C(H) domain. Finally, we discuss the flexibility of the MD/PCA model in relation with the static x-ray structure. A movement of the antibody toward the dimerization domain of the ErbB2 receptor is reported for the first time. This finding could have important consequences on the biological action of the monoclonal antibody.

  • 28.
    Franco-Gonzalez, Juan Felipe
    et al.
    Biophym, Macromolecular Physics Department, Instituto de Estructura de la Materia, CSIC, Serrano 113-bis, 28006, Madrid, Spain .
    Ramos, Javier
    Biophym, Macromolecular Physics Department, Instituto de Estructura de la Materia, CSIC, Serrano 113-bis, 28006, Madrid, Spain .
    Cruz, Victor L
    Biophym, Macromolecular Physics Department, Instituto de Estructura de la Materia, CSIC, Serrano 113-bis, 28006, Madrid, Spain .
    Martinez-Salazar, Javier
    Biophym, Macromolecular Physics Department, Instituto de Estructura de la Materia, CSIC, Serrano 113-bis, 28006, Madrid, Spain .
    Exploring the dynamics and interaction of a full ErbB2 receptor and Trastuzumab-Fab antibody in a lipid bilayer model using Martini coarse-grained force field.2014In: Journal of Computer-Aided Molecular Design, ISSN 0920-654X, E-ISSN 1573-4951, Vol. 28, no 11, p. 1093-1107Article in journal (Refereed)
    Abstract [en]

    Coarse grained (CG) modeling has been applied to study the influence of the Trastuzumab monoclonal antibody on the structure and dynamics of the full ErbB2 receptor dimer, including the lipid bilayer. The usage of CG models to study such complexes is almost mandatory, at present, due to the large size of the whole system. We will show that the Martini model performs satisfactorily well, giving results well-matched with those obtained by atomistic models as well as with the experimental information existing on homolog receptors. For example, the extra and intracellular domains approach the bilayer surface in both the monomer and dimer cases. The Trastuzumab-Fab hinders the interaction of the receptors with the lipid bilayer. Another interesting effect of the antibody is the disruption of the antiparallel arrangement of the juxtamembrane segments in the dimer case. These findings might help to understand the effect of the antibody on the receptor bioactivity.

  • 29.
    Franco-Gonzalez, Juan Felipe
    et al.
    BIOPHYM, Macromolecular Physics Department, Instituto de Estructura de la Materia, CSIC, Serrano 113 bis, 28006, Madrid, Spain .
    Ramos, Javier
    BIOPHYM, Macromolecular Physics Department, Instituto de Estructura de la Materia, CSIC, Serrano 113 bis, 28006, Madrid, Spain .
    Cruz, Victor L
    BIOPHYM, Macromolecular Physics Department, Instituto de Estructura de la Materia, CSIC, Serrano 113 bis, 28006, Madrid, Spain .
    Martínez-Salazar, Javier
    BIOPHYM, Macromolecular Physics Department, Instituto de Estructura de la Materia, CSIC, Serrano 113 bis, 28006, Madrid, Spain .
    Simulation of homology models for the extracellular domains (ECD) of ErbB3, ErbB4 and the ErbB2-ErbB3 complex in their active conformations.2013In: Journal of Molecular Modeling, ISSN 1610-2940, E-ISSN 0948-5023, Vol. 19, no 2, p. 931-941Article in journal (Refereed)
    Abstract [en]

    Epidermal growth factor receptors (EGFR) are associated with a number of biological processes and are becoming increasingly recognized as important therapeutic targets against cancer. In this work, we provide models based on homology for the extracellular domains (ECD) of ErbB3 and ErbB4 in their active conformations, including a Heregulin ligand, followed by further refinement of the models by molecular dynamics simulations at atomistic scale. We compare the results with a model built for ErbB2 based on crystallographic information and analyze the common features observed among members of the family, namely, the periscope movement of the dimerization arm and the hinge displacement of domain IV. Finally, we refine a model for the interaction of the ECDs corresponding to a ErbB2-ErbB3 heterodimer, which is widely recognized to have a high impact in cancer development.

  • 30.
    Gelmi, Amy
    et al.
    Linköping University, Faculty of Science & Engineering. Linköping University, Department of Physics, Chemistry and Biology, Biosensors and Bioelectronics. Imperial Coll London, England.
    Cieslar-Pobuda, Artur
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Silesian Technical University, Poland.
    de Muinck, Ebo
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Los, Marek Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Pomeranian Medical University, Poland.
    Rafat, Mehrdad
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    Jager, Edwin
    Linköping University, Department of Physics, Chemistry and Biology, Biosensors and Bioelectronics. Linköping University, Faculty of Science & Engineering.
    Direct Mechanical Stimulation of Stem Cells: A Beating Electromechanically Active Scaffold for Cardiac Tissue Engineering2016In: Advanced Healthcare Materials, ISSN 2192-2640, E-ISSN 2192-2659, Vol. 5, no 12, p. 1471-1480Article in journal (Refereed)
    Abstract [en]

    The combination of stem cell therapy with a supportive scaffold is a promising approach to improving cardiac tissue engineering. Stem cell therapy can be used to repair nonfunctioning heart tissue and achieve myocardial regeneration, and scaffold materials can be utilized in order to successfully deliver and support stem cells in vivo. Current research describes passive scaffold materials; here an electroactive scaffold that provides electrical, mechanical, and topographical cues to induced human pluripotent stem cells (iPS) is presented. The poly(lactic-co-glycolic acid) fiber scaffold coated with conductive polymer polypyrrole (PPy) is capable of delivering direct electrical and mechanical stimulation to the iPS. The electroactive scaffolds demonstrate no cytotoxic effects on the iPS as well as an increased expression of cardiac markers for both stimulated and unstimulated protocols. This study demonstrates the first application of PPy as a supportive electroactive material for iPS and the first development of a fiber scaffold capable of dynamic mechanical actuation.

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  • 31.
    Gil, Maria A.
    et al.
    Univ Murcia, Spain; Inst Biomed Res Murcia, Spain.
    Cambra, Josep M.
    Techn Univ Munich, Germany.
    Rodriguez-Martinez, Heriberto
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Cuello, Cristina
    Univ Murcia, Spain; Inst Biomed Res Murcia, Spain.
    Parrilla, Inmaculada
    Univ Murcia, Spain; Inst Biomed Res Murcia, Spain.
    Martinez, Emilio A.
    Univ Murcia, Spain; Inst Biomed Res Murcia, Spain.
    In-depth proteome characterization of endometrium and extraembryonic membranes during implantation in pig2024In: JOURNAL OF ANIMAL SCIENCE AND BIOTECHNOLOGY, ISSN 1674-9782, Vol. 15, no 1, article id 43Article in journal (Refereed)
    Abstract [en]

    BackgroundProteome characterization of the porcine endometrium and extraembryonic membranes is important to understand mother-embryo cross-communication. In this study, the proteome of the endometrium and chorioallantoic membrane was characterized in pregnant sows (PS) during early gestation (d 18 and 24 of gestation) and in the endometrium of non-pregnant sows (NPS) during the same days using LC-MS/MS analysis. The UniProtKB database and ClueGO were used to obtain functional Gene Ontology annotations and biological and functional networks, respectively.ResultsOur analysis yielded 3,254 and 3,457 proteins identified in the endometrium of PS and NPS, respectively; of these, 1,753 being common while 1,501 and 1,704 were exclusive to PS and NPS, respectively. In addition, we identified 3,968 proteins in the extraembryonic membranes of PS. Further analyses of function revealed some proteins had relevance for the immune system process and biological adhesion in endometrium while the embryonic chorion displayed abundance of proteins related to cell adhesion and cytoskeletal organization, suggesting they dominated the moment of endometrial remodeling, implantation and adhesion of the lining epithelia. Data are available via ProteomeXchange with identifier PXD042565.ConclusionThis is the first in-depth proteomic characterization of the endometrium and extraembryonic membranes during weeks 3 to 4 of gestation; data that contribute to the molecular understanding of the dynamic environment during this critical period, associated with the majority of pregnancy losses.

  • 32.
    Gryszel, Maciej
    et al.
    Linköping University, Department of Science and Technology, Laboratory of Organic Electronics. Linköping University, Faculty of Science & Engineering.
    Jakesova, Marie
    Brno Univ Technol, Czech Republic.
    Vu, Xuan Thang
    Rhein Westfal TH Aachen, Germany.
    Ingebrandt, Sven
    Rhein Westfal TH Aachen, Germany.
    Glowacki, Eric Daniel
    Brno Univ Technol, Czech Republic.
    Elevating Platinum to Volumetric Capacitance: High Surface Area Electrodes through Reactive Pt Sputtering2024In: Advanced Healthcare Materials, ISSN 2192-2640, E-ISSN 2192-2659Article in journal (Refereed)
    Abstract [en]

    Platinum is the most widespread electrode material used for implantable biomedical and neuroelectronic devices, motivating exploring ways to improve its performance and understand its fundamental properties. Using reactive magnetron sputtering, PtOx is prepared, which upon partial reduction yields a porous thin-film form of platinum with favorable properties, notably record-low impedance values outcompeting other reports for platinum-based electrodes. It is established that its high electrochemical capacitance scales with thickness, in the way of volumetric capacitor materials like IrOx and poly(3,4-ethylenedioxythiophene), PEDOT. Unlike these two well-known analogs, however, it is found that PtOx capacitance is not caused by reversible pseudofaradaic reactions but rather due to high surface area. In contrast to IrOx, PtOx is not a reversible valence-change oxide, but rather a porous form of platinum. The findings show that this oxygen-containing form of Pt can place Pt electrodes on a level competitive with IrOx and PEDOT. Due to its relatively low cost and ease of preparation, PtOx can be a good choice for microfabricated bioelectronic devices. Platinum is used in many medical implants, but lags behind next-generation electrode materials in performance. How sputtered platinum oxide is a microfabricatable thin film material that provides bioelectronics electrodes with volumetric capacitance and low impedance that tweaks platinum to compete at the level of conducting polymers and IrOx is shown. image

  • 33.
    Herberthson, Magnus
    et al.
    Linköping University, Department of Mathematics, Mathematics and Applied Mathematics. Linköping University, Faculty of Science & Engineering.
    Yolcu, Cem
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Knutsson, Hans
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Westin, Carl-Fredrik
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. Harvard Med Sch, MA 02115 USA.
    Özarslan, Evren
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Orientationally-averaged diffusion-attenuated magnetic resonance signal for locally-anisotropic diffusion2019In: Scientific Reports, E-ISSN 2045-2322, Vol. 9, article id 4899Article in journal (Refereed)
    Abstract [en]

    Diffusion-attenuated MR signal for heterogeneous media has been represented as a sum of signals from anisotropic Gaussian sub-domains to the extent that this approximation is permissible. Any effect of macroscopic (global or ensemble) anisotropy in the signal can be removed by averaging the signal values obtained by differently oriented experimental schemes. The resulting average signal is identical to what one would get if the micro-domains are isotropically (e.g., randomly) distributed with respect to orientation, which is the case for "powdered" specimens. We provide exact expressions for the orientationally-averaged signal obtained via general gradient waveforms when the microdomains are characterized by a general diffusion tensor possibly featuring three distinct eigenvalues. This extends earlier results which covered only axisymmetric diffusion as well as measurement tensors. Our results are expected to be useful in not only multidimensional diffusion MR but also solid-state NMR spectroscopy due to the mathematical similarities in the two fields.

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  • 34.
    Hernandez, Frank Jeyson
    et al.
    Department of Chemical Engineering, Universitat Rovira i Virgili, Tarragona, Spain.
    Dondapati, Srujan Kumar
    Photonics and Optoelectronics Group, Physics Department and Center for Nanoscience CeNS, Ludwig-Maximilians-Universität München, Munich, Germany.
    Ozalp, V Cengiz
    Bioengineering and Bioelectrochemistry Group, Department of Chemical Engineering, Universitat Rovira i Virgili, Tarragona, Spain.
    Pinto, Alessandro
    Bioengineering and Bioelectrochemistry Group, Department of Chemical Engineering, Universitat Rovira i Virgili, Tarragona, Spain.
    O'Sullivan, Ciara K
    Bioengineering and Bioelectrochemistry Group, Department of Chemical Engineering, Universitat Rovira i Virgili, Tarragona, Spain.
    Klar, Thomas A
    Institute of Physics and Institute of Micro and Nanotechnologies, Technical University of Ilmenau, Ilmenau, Germany.
    Katakis, Ioannis
    Bioengineering and Bioelectrochemistry Group, Department of Chemical Engineering, Universitat Rovira i Virgili, Tarragona, Spain.
    Label free optical sensor for Avidin based on single gold nanoparticles functionalized with aptamers2009In: Journal of Biophotonics, ISSN 1864-063X, E-ISSN 1864-0648, Vol. 2, no 4, p. 227-231Article in journal (Refereed)
    Abstract [en]

    Optical spectroscopy of a single gold nanoparticle, functionalized with an aptamer, is used to sense the specific binding of avidin. Herewith, the field of single noble metal nanoparticle biosensors is extended to the important field of aptamer based assays. The sensitivity of this initial, but not yet optimized apta-nano-sensor is in the range of 20 nM. Due to its nanoscopic size, this single nanoparticle based apta-sensor may be used in nanoscopic volumes such as in array type assays or even inside cells.

  • 35.
    Hook, Fredrik
    et al.
    Lund University, Sweden; Chalmers, Sweden.
    Stengel, Gudrun
    Division of Solid State Physics, Lund University, Lund, SE-22100, Sweden .
    Dahlin, Andreas B.
    Lund University, Sweden; Chalmers, Sweden.
    Gunnarsson, Anders
    Division of Solid State Physics, Lund University, Lund, SE-22100, Sweden .
    Jonsson, Magnus P.
    Division of Solid State Physics, Lund University, Lund, SE-22100, Sweden .
    Jonsson, Peter
    Division of Solid State Physics, Lund University, Lund, SE-22100, Sweden .
    Reimhult, Erik
    Department of Applied Physics, Chalmers University of Technology, Göteborg, SE-41296, Sweden .
    Simonsson, Lisa
    Division of Solid State Physics, Lund University, Lund, SE-22100, Sweden .
    Svedhem, Sofia
    Department of Applied Physics, Chalmers University of Technology, Göteborg, SE-41296, Sweden .
    Supported lipid bilayers, tethered lipid vesicles, and vesicle fusion investigated using gravimetric, plasmonic, and microscopy techniques2008In: Biointerphases, ISSN 1934-8630, E-ISSN 1559-4106, Vol. 3, no 2, p. FA108-FA116Article in journal (Refereed)
    Abstract [en]

    This article summarizes our most recent contributions to the rapidly growing field of supported lipid assemblies with emphasis on current studies addressing both fundamental and applied aspects of supported lipid bilayer (SLB) and tethered lipid vesicles (TLVs) to be utilized in sensing applications. The new insights obtained from combining the quartz crystal microbalance with dissipation monitoring technique with surface plasmon resonance are described, and we also present recent studies in which nanoplasmonic sensing has been used in studies of SLBs and TLVs. To gain full control over the spatial arrangement of TLVs in both two and three dimensions, we have developed a method for site-selective and sequence-specific sorting of DNA-tagged vesicles to surfaces modified with complementary DNA. The combination of this method with nanoplasmonic sensing formats is covered as well as the possibility of using DNA-modified vesicles for the detection of unlabeled DNA targets on the single-molecule level. Finally, a new method for membrane fusion induced by hybridization of vesicle-anchored DNA is demonstrated, including new results on content mixing obtained with vesicle populations encapsulating short, complementary DNA strands.

  • 36.
    Hoshi, T.
    et al.
    Department of Physiology, The University of Pennsylvania, Philadelphia, Pennsylvania, USA.
    Pantazis, Antonios
    Division of Molecular Medicine, Department of Anesthesiology, University of California, Los Angeles, USA.
    Olcese, Riccardo
    Division of Molecular Medicine, Department of Anesthesiology, and Brain Research Institute, and Cardiovascular Research Laboratories, University of California, Los Angeles, USA.
    Transduction of Voltage and Ca2+ Signals by Slo1 BK Channels2013In: Physiology (Bethesda), ISSN 1548-9213, Vol. 28, no 3, p. 172-189Article, review/survey (Refereed)
    Abstract [en]

    Large-conductance Ca2+- and voltage-gated K+ channels are activated by an increase in intracellular Ca2+ concentration and/or depolarization. The channel activation mechanism is well described by an allosteric model encompassing the gate, voltage sensors, and Ca2+ sensors, and the model is an excellent framework to understand the influences of auxiliary β and γ subunits and regulatory factors such as Mg2+. Recent advances permit elucidation of structural correlates of the biophysical mechanism.

  • 37.
    Hutchins, George H.
    et al.
    Vrije Univ Amsterdam, Netherlands.
    Kiehstaller, Sebastian
    Incircular BV, Netherlands.
    Poc, Pascal
    Vrije Univ Amsterdam, Netherlands.
    Lewis, Abigail H.
    Vrije Univ Amsterdam, Netherlands.
    Oh, Jisun
    Vrije Univ Amsterdam, Netherlands.
    Sadighi, Raya
    Vrije Univ Amsterdam, Netherlands.
    Pearce, Nicholas
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering. Vrije Univ Amsterdam, Netherlands.
    Ibrahim, Mohamed
    Vrije Univ Amsterdam, Netherlands.
    Drienovska, Ivana
    Vrije Univ Amsterdam, Netherlands.
    Rijs, Anouk M.
    Vrije Univ Amsterdam, Netherlands.
    Neubacher, Saskia
    Incircular BV, Netherlands.
    Hennig, Sven
    Vrije Univ Amsterdam, Netherlands.
    Grossmann, Tom N.
    Vrije Univ Amsterdam, Netherlands.
    Covalent bicyclization of protein complexes yields durable quaternary structures2024In: Chem, ISSN 2451-9308, E-ISSN 2451-9294, Vol. 10, no 2Article in journal (Refereed)
    Abstract [en]

    Proteins are essential biomolecules and central to biotechnological applications. In many cases, assembly into higher -order structures is a prerequisite for protein function. Under conditions relevant for applications, protein integrity is often challenged, resulting in disassembly, aggregation, and loss of function. The stabilization of quaternary structure has proven challenging, particularly for trimeric and higher -order complexes, given the complexity of involved interand intramolecular interaction networks. Here, we describe the chemical bicyclization of homotrimeric protein complexes, thereby increasing protein resistance toward thermal and chemical stress. This approach involves the structure -based selection of cross -linking sites, their variation to cysteine, and a subsequent reaction with a triselectrophilic agent to form a protein assembly with bicyclic topology. Besides overall increased stability, we observe resistance toward aggregation and greatly prolonged shelf life. This bicyclization strategy gives rise to unprecedented protein chain topologies and can enable new biotechnological and biomedical applications.

  • 38.
    Janssen, Xander J. A.
    et al.
    Delft University of Technology, Netherlands.
    Jonsson, Magnus P.
    Delft University of Technology, Netherlands.
    Plesa, Calin
    Delft University of Technology, Netherlands.
    Soni, Gautam V.
    Delft University of Technology, Netherlands.
    Dekker, Cees
    Delft University of Technology, Netherlands.
    Dekker, Nynke H.
    Delft University of Technology, Netherlands.
    Rapid manufacturing of low-noise membranes for nanopore sensors by trans-chip illumination lithography2012In: Nanotechnology, ISSN 0957-4484, E-ISSN 1361-6528, Vol. 23, no 47, article id 475302Article in journal (Refereed)
    Abstract [en]

    In recent years, the concept of nanopore sensing has matured from a proof-of-principle method to a widespread, versatile technique for the study of biomolecular properties and interactions. While traditional nanopore devices based on a nanopore in a single layer membrane supported on a silicon chip can be rapidly fabricated using standard microfabrication methods, chips with additional insulating layers beyond the membrane region can provide significantly lower noise levels, but at the expense of requiring more costly and time-consuming fabrication steps. Here we present a novel fabrication protocol that overcomes this issue by enabling rapid and reproducible manufacturing of low-noise membranes for nanopore experiments. The fabrication protocol, termed trans-chip illumination lithography, is based on illuminating a membrane-containing wafer from its backside such that a photoresist (applied on the wafers top side) is exposed exclusively in the membrane regions. Trans-chip illumination lithography permits the local modification of membrane regions and hence the fabrication of nanopore chips containing locally patterned insulating layers. This is achieved while maintaining a well-defined area containing a single thin membrane for nanopore drilling. The trans-chip illumination lithography method achieves this without relying on separate masks, thereby eliminating time-consuming alignment steps as well as the need for a mask aligner. Using the presented approach, we demonstrate rapid and reproducible fabrication of nanopore chips that contain small (12 mu m x 12 mu m) free-standing silicon nitride membranes surrounded by insulating layers. The electrical noise characteristics of these nanopore chips are shown to be superior to those of simpler designs without insulating layers and comparable in quality to more complex designs that are more challenging to fabricate.

  • 39.
    Johansson, Patrik
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, The Institute of Technology.
    Jullesson, David
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, The Institute of Technology.
    Elfwing, Anders
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, Faculty of Science & Engineering.
    Liin, Sara
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Musumeci, Chiara
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, Faculty of Science & Engineering.
    Zeglio, Erica
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, Faculty of Science & Engineering.
    Elinder, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Solin, Niclas
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, Faculty of Science & Engineering.
    Inganäs, Olle
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, Faculty of Science & Engineering.
    Electronic polymers in lipid membranes2015In: Scientific Reports, E-ISSN 2045-2322, Vol. 5, no 11242Article in journal (Refereed)
    Abstract [en]

    Electrical interfaces between biological cells and man-made electrical devices exist in many forms, but it remains a challenge to bridge the different mechanical and chemical environments of electronic conductors (metals, semiconductors) and biosystems. Here we demonstrate soft electrical interfaces, by integrating the metallic polymer PEDOT-S into lipid membranes. By preparing complexes between alkyl-ammonium salts and PEDOT-S we were able to integrate PEDOT-S into both liposomes and in lipid bilayers on solid surfaces. This is a step towards efficient electronic conduction within lipid membranes. We also demonstrate that the PEDOT-S@alkyl-ammonium: lipid hybrid structures created in this work affect ion channels in the membrane of Xenopus oocytes, which shows the possibility to access and control cell membrane structures with conductive polyelectrolytes.

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  • 40.
    Johansson-Åkhe, Isak
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Mirabello, Claudio
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Wallner, Björn
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    InterPep2: global peptide-protein docking using interaction surface templates2020In: Bioinformatics, ISSN 1367-4803, E-ISSN 1367-4811, Vol. 36, no 8, p. 2458-2465Article in journal (Refereed)
    Abstract [en]

    Motivation: Interactions between proteins and peptides or peptide-like intrinsically disordered regions are involved in many important biological processes, such as gene expression and cell life-cycle regulation. Experimentally determining the structure of such interactions is time-consuming and difficult because of the inherent flexibility of the peptide ligand. Although several prediction-methods exist, most are limited in performance or availability. Results: InterPep2 is a freely available method for predicting the structure of peptide-protein interactions. Improved performance is obtained by using templates from both peptide-protein and regular protein-protein interactions, and by a random forest trained to predict the DockQ-score for a given template using sequence and structural features. When tested on 252 bound peptide-protein complexes from structures deposited after the complexes used in the construction of the training and templates sets of InterPep2, InterPep2-Refined correctly positioned 67 peptides within 4.0 angstrom LRMSD among top10, similar to another state-of-the-art template-based method which positioned 54 peptides correctly. However, InterPep2 displays a superior ability to evaluate the quality of its own predictions. On a previously established set of 27 non-redundant unbound-to-bound peptide-protein complexes, InterPep2 performs on-par with leading methods. The extended InterPep2-Refined protocol managed to correctly model 15 of these complexes within 4.0 angstrom LRMSD among top10, without using templates from homologs. In addition, combining the template-based predictions from InterPep2 with ab initio predictions from PIPER-FlexPepDock resulted in 22% more near-native predictions compared to the best single method (22 versus 18).

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  • 41.
    Johansson-Åkhe, Isak
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Mirabello, Claudio
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Wallner, Björn
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Predicting protein-peptide interaction sites using distant protein complexes as structural templates2019In: Scientific Reports, E-ISSN 2045-2322, Vol. 9, article id 4267Article in journal (Refereed)
    Abstract [en]

    Protein-peptide interactions play an important role in major cellular processes, and are associated with several human diseases. To understand and potentially regulate these cellular function and diseases it is important to know the molecular details of the interactions. However, because of peptide flexibility and the transient nature of protein-peptide interactions, peptides are difficult to study experimentally. Thus, computational methods for predicting structural information about protein-peptide interactions are needed. Here we present InterPep, a pipeline for predicting protein-peptide interaction sites. It is a novel pipeline that, given a protein structure and a peptide sequence, utilizes structural template matches, sequence information, random forest machine learning, and hierarchical clustering to predict what region of the protein structure the peptide is most likely to bind. When tested on its ability to predict binding sites, InterPep successfully pinpointed 255 of 502 (50.7%) binding sites in experimentally determined structures at rank 1 and 348 of 502 (69.3%) among the top five predictions using only structures with no significant sequence similarity as templates. InterPep is a powerful tool for identifying peptide-binding sites; with a precision of 80% at a recall of 20% it should be an excellent starting point for docking protocols or experiments investigating peptide interactions. The source code for InterPred is available at http://wallnerlab.org/InterPep/.

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  • 42.
    Jonsson, Bengt-Harald
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Liljas, Anders
    Lund Univ, Sweden.
    Comments to the Editor Due to the Response by the Supuran Group to Our Article2021In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 120, no 1, p. 182-183Article in journal (Other academic)
    Abstract [en]

    n/a

  • 43.
    Jonsson, Magnus P.
    et al.
    Department of Applied Physics, Chalmers University of Technology, SE-41296 Gothenburg, Sweden.
    Dahlin, Andreas B.
    Department of Applied Physics, Chalmers University of Technology, SE-41296 Gothenburg, Sweden.
    Feuz, Laurent
    Department of Applied Physics, Chalmers University of Technology, SE-41296 Gothenburg, Sweden.
    Petronis, Sarunas
    Department of Applied Physics, Chalmers University of Technology, SE-41296 Gothenburg, Sweden.
    Hook, Fredrik
    Department of Applied Physics, Chalmers University of Technology, SE-41296 Gothenburg, Sweden.
    Locally Functionalized Short-Range Ordered Nanoplasmonic Pores for Bioanalytical Sensing2010In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 82, no 5, p. 2087-2094Article in journal (Refereed)
    Abstract [en]

    Nanoplasmonic sensors based on short-range ordered nano-holes in thin metal films and discrete metal nanoparticles are known to provide similar sensing performance. However, a perforated metal film is unique in the sense that the holes can be designed to penetrate through the substrate, thereby also fulfilling the role of nanofluidic channels. This paper presents a bioanalytical sensing concept based on short-range ordered nanoplasmonic pores (diameter 150 nm) penetrating through a thin (around 250 nm) multilayer membrane composed of gold and silicon nitride (SiN) that is Supported on a Si wafer. Also, a fabrication scheme that enables parallel production of multiple (more than 50) separate sensor chips or more than 1000 separate nanoplasmonic membranes on it single wafer is presented. Together with the localization of the sensitivity to within such short-range ordered nanoholes, the structure provides it two-dimensional nanofluidic network, sized in the order of 100 x 100 mu m(2), with nanoplasmon active regions localized to each individual nanochannel. A material-specific surface-modification scheme was developed to promote specific binding of target molecules on the optically active gold regions only, while suppressing nonspecific adsorption on SiN. Using this protocol, and by monitoring the temporal variation in the plasmon resonance of the structure, we demonstrate flow-through nanoplasmonic sensing of specific biorecognition reactions with a signal-to-noise ratio of around 50 at a temporal resolution below 190 ms. With flow, the uptake was demonstrated to be at least 1 order of magnitude faster than under stagnant conditions, while still keeping the sample consumption at a minimum.

  • 44.
    Jonsson, Magnus P.
    et al.
    DiVision of Solid State Physics, Lund UniVersity, SE-22100 Lund, Sweden.
    Jonsson, Peter
    DiVision of Solid State Physics, Lund UniVersity, SE-22100 Lund, Sweden.
    Dahlin, Andreas B.
    DiVision of Solid State Physics, Lund UniVersity, SE-22100 Lund, Sweden.
    Hook, Fredrik
    DiVision of Solid State Physics, Lund UniVersity, SE-22100 Lund, Sweden.
    Supported lipid bilayer formation and lipid-membrane-mediated biorecognition reactions studied with a new nanoplasmonic sensor template2007In: Nano letters (Print), ISSN 1530-6984, E-ISSN 1530-6992, Vol. 7, no 11, p. 3462-3468Article in journal (Refereed)
    Abstract [en]

    This paper presents the use of the localized surface plasmon resonance (LSPR) sensor concept to probe the formation of macroscopic and laterally mobile supported lipid bilayers (SLBs) on SiO(x)-encapsulated nanohole-containing Au and Ag films. A comparison between Au- and Ag-based sensor templates demonstrates a higher sensitivity for Au-based templates with respect to both bulk and interfacial refractive index (RI) changes in aqueous solution. The lateral mobility of SLBs formed on the SiO(x)-rencapsulated nanohole templates was analyzed using fluorescence recovery after photobleaching (FRAP), demonstrating essentially complete (greater than96%) recovery, but a reduction in diffusivity of about 35% compared with SLBs formed on flat SiO(x) substrates. Furthermore, upon SLB formation, the temporal variation in extinction peak position of the LSPR active templates display a characteristic shape, illustrating what, to the best of our knowledge, is the first example where the nanoplasmonic concept is shown capable of probing biomacromolecular structural changes without the introduction of labels. With a signal-to-noise ratio better than 5 X 10(2) upon protein binding to the cell-membrane mimics, the sensor concept is also proven competitive with state-of-the-art label-free sensors.

  • 45.
    Jonsson, Magnus P.
    et al.
    Division of Solid State Physics, Department of Physics, Lund University, Lund, Sweden..
    Jonsson, Peter
    Division of Solid State Physics, Department of Physics, Lund University, Lund, Sweden..
    Hook, Fredrik
    Division of Solid State Physics, Department of Physics, Lund University, Lund, Sweden..
    Simultaneous Nanoplasmonic and Quartz Crystal Microbalance Sensing: Analysis of Biomolecular Conformational Changes and Quantification of the Bound Molecular Mass2008In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 80, no 21, p. 7988-7995Article in journal (Refereed)
    Abstract [en]

    This paper presents a study of supported lipid bilayer (SIB) formation and subsequent protein binding using a sensor that combines localized surface plasmon resonance (LSPR) and quartz crystal microbalance with dissipation (QCM-D) monitoring. The LSPR activity arises from silicon oxide (SiOx) coated nanometric apertures in a thin gold film, which also serves as the active electrode of a QCM-D crystal. Both transducer principles provide signatures for the formation of a SLB upon adsorption and subsequent rupture of adsorbed lipid vesicles. However, the two techniques are sensitive over different regions of the sample: LSPR primarily inside and on the rim of the holes and QCM-D primarily on the planar areas between the holes. Although the dimension of the lipid vesicles is on the same order as the dimension of the nanoholes, it is concluded from the response of the combined system that vesicle rupture in the nanoholes and on the planar region between the holes is synchronized. Furthermore, by determining the thickness of the SLB from the QCM-D response, the characteristic decay length of the LSPR field intensity could be determined. This made it possible not only to determine the mass and refractive index of the homogeneous SLB but also to postulate a generic means to quantify the LSPR response in terms of mass-uptake also for nonhomogeneous films. This is exemplified by measuring the adsorbed lipid mass during vesicle adsorption, yielding the critical lipid vesicle coverage at which spontaneous rupture into a planar bilayer occurs. The generic applicability and versatility of the method is demonstrated from specific protein binding to a functionalized SLB. From the absolute refractive index of the protein, provided from the LSPR data alone, it was possible to determine both the effective thickness of the protein film and the molecular mass (or number) of bound protein.

  • 46.
    Jonsson, Peter
    et al.
    Department of Applied Physics, Chalmers University of Technology, SE-41296 Gothenburg, Sweden.
    Jonsson, Magnus P.
    Department of Applied Physics, Chalmers University of Technology, SE-41296 Gothenburg, Sweden.
    Hook, Fredrik
    Department of Applied Physics, Chalmers University of Technology, SE-41296 Gothenburg, Sweden.
    Sealing of Submicrometer Wells by a Shear-Driven Lipid Bilayer2010In: Nano letters (Print), ISSN 1530-6984, E-ISSN 1530-6992, Vol. 10, no 5, p. 1900-1906Article in journal (Refereed)
    Abstract [en]

    A supported lipid bilayer (SLB) was formed in a microfluidic channel by vesicle fusion. The SLB, formed on a flat part of the surface, was driven by the shear forces of a bulk flow above the SLB to a part of the surface with embedded submicrometer wells. When using a bulk solution with a pH of 9.5 the advancing lipid bilayer sealed the wells, creating free-spanning membranes, whereas at a pH of 8.0 the SLB instead followed the contour of the wells.

  • 47.
    Jury, Michael
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Matthiesen, Isabelle
    KTH Royal Institute of Technology, Stockholm, Sweden.
    Boroojeni, Fatemeh Rasti
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Ludwig, Saskia L.
    KTH Royal Institute of Technology, Stockholm, Sweden.
    Civitelli, Livia
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering. University of Oxford, England.
    Winkler, Thomas E.
    KTH Royal Institute of Technology, Stockholm, Sweden; Institute of Microtechnology, Center of Pharmaceutical Engineering, Technische Universität Braunschweig, Braunschweig, Germany.
    Selegård, Robert
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Herland, Anna
    Division of Micro and Nanosystems, KTH Royal Institute of Technology, Stockholm, Sweden; Department of Neuroscience, Karolinska Institute, Solna, Sweden; Division of Nanobiotechnology, Department of Protein Science, Science for Life Laboratory, KTH Royal Institute of Technology, Stockholm, Sweden.
    Aili, Daniel
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Bioorthogonally Cross-Linked Hyaluronan-Laminin Hydrogels for 3D Neuronal Cell Culture and Biofabrication2022In: Advanced Healthcare Materials, ISSN 2192-2640, E-ISSN 2192-2659, Vol. 11, no 11, article id 2102097Article in journal (Refereed)
    Abstract [en]

    Laminins (LNs) are key components in the extracellular matrix of neuronal tissues in the developing brain and neural stem cell niches. LN-presenting hydrogels can provide a biologically relevant matrix for the 3D culture of neurons toward development of advanced tissue models and cell-based therapies for the treatment of neurological disorders. Biologically derived hydrogels are rich in fragmented LN and are poorly defined concerning composition, which hampers clinical translation. Engineered hydrogels require elaborate and often cytotoxic chemistries for cross-linking and LN conjugation and provide limited possibilities to tailor the properties of the materials. Here a modular hydrogel system for neural 3D cell cultures, based on hyaluronan and poly(ethylene glycol), that is cross-linked and functionalized with human recombinant LN-521 using bioorthogonal copper-free click chemistry, is shown. Encapsulated human neuroblastoma cells demonstrate high viability and grow into spheroids. Long-term neuroepithelial stem cells (lt-NES) cultured in the hydrogels can undergo spontaneous differentiation to neural fate and demonstrate significantly higher viability than cells cultured without LN. The hydrogels further support the structural integrity of 3D bioprinted structures and maintain high viability of bioprinted and syringe extruded lt-NES, which can facilitate biofabrication and development of cell-based therapies.

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  • 48.
    Karlsson, Linda
    Linköping University, Department of Physics, Measurement Technology, Biology and Chemistry. Linköping University, The Institute of Technology.
    Biomolecular Interactions with Porous Silicon2003Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    One common problem when putting something inside the body is a fast response from the body defending it from the intruder. Here the researchers are struggling with finding biocompatible materials, which act in a predicted and non-harmful way. In the drug delivery area the idea is to find a good solution of giving a patient its daily medication in a convenient way. The ideal would be to have a unit that could deliver the drug automatically when needed in the dose needed. By high trough putscreening, finding of potential drugs or molecules related to diseases takes much less time. Here a large surface area to which the substance of interest can attach is preferable to be able to use as little analyte as possible and still have a high sensitivity.

    To be able to realize the applications mentioned above a basic understanding of how proteins interact with surfaces must be developed.The aim of this thesis has been to investigate the adsorption of proteins into and on porous silicon.

    Porous silicon was chosen as the porous material to work with because porous silicon has been shown to be bioactive and produce hydroxyapatite upon incubation in simulated body fluid. It is also a material with large surface area, which is convenient to use in the chiparea as well as in drug delivery.

    Gradients in pore size and porous layer thickness were etched in silicon and used in protein adsorption experiments together with homogeneous porous layers. The adsorbed amounts of protein were determined at different pH, different protein concentrations as well as for porous silicon prepared with different etching conditions.

    The results show that the morphology of the porous layer influence the protein uptake, indicating that more protein is found for larger pore sizes as well as for thicker porous layers. A minimum pore size of 5.5 nm in radius was found for albumin penetration. An increase in protein concentration up to 10 mg/ml albumin resulted in more proteins loaded into the porous silicon layer. The refractive index spectrum of carbonic anhydrase and location of the protein in porous silicon were also determined.

    List of papers
    1. Back-side etching A tool for making morphology gradients in porous silicon
    Open this publication in new window or tab >>Back-side etching A tool for making morphology gradients in porous silicon
    2002 (English)In: Journal of the Electrochemical Society, ISSN 0013-4651, E-ISSN 1945-7111, Vol. 149, no 12Article in journal (Refereed) Published
    Abstract [en]

    A new method for preparing morphology gradients in electrochemically etched porous silicon layers in presented. The idea is to etch on the back side of the anode and thus utilize and inhomogenous electric field to control the pore size along a surface. The etching procedure resulted in a complex gradient in pore size, porosity, and porous layer thickness, which was studied by spectroscopic ellipsometry and scanning electron microscopy. The gradients are of interest, e.g., for biomaterials research, bio-sensor applications, and for basic studies of adsorption of organic molecules, like proteins. In order to investigate the potential of the gradient surfaces for protein adsorption studies, these were exposed to human serum albumin, and a gradient in the amount of adsorbed protein was observed.

    National Category
    Engineering and Technology
    Identifiers
    urn:nbn:se:liu:diva-46823 (URN)10.1149/1.1519851 (DOI)
    Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2021-09-17
    2. Adsorption of human serum albumin in porous silicon gradients
    Open this publication in new window or tab >>Adsorption of human serum albumin in porous silicon gradients
    2003 (English)Conference paper, Published paper (Other academic)
    Abstract [en]

    Backside etching has been utilized to produce gradients of pore size and layer thickness in porous silicon. Human serum albumin (HSA) was adsorbed on such gradients at two different pH values: 4.9, the pI of HSA, and 7.4, the physiological pH. The samples were investigated by scanning electron microscopy, spectroscopic ellipsometry, and autoradiography. The results show that the protein adsorbed displays a gradient along with the pore size and the thickness gradient. The higher than current density used during etching, the more sway-back shaped curves were seen for the protein adsorption pattern, independent of pH. When 50 mA/cm2 current density was used during etching, the quota between the maximal intensity value and the plateau value seen after adsorption of the HSA increased for pH 7.4.

    National Category
    Engineering and Technology
    Identifiers
    urn:nbn:se:liu:diva-46654 (URN)10.1002/pssa.200306518 (DOI)
    Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2021-09-17
    3. Penetration and loading of human serum albumin in porous silicon layers with different pore sizes and thicknesses
    Open this publication in new window or tab >>Penetration and loading of human serum albumin in porous silicon layers with different pore sizes and thicknesses
    2003 (English)In: Journal of Colloid and Interface Science, ISSN 0021-9797, E-ISSN 1095-7103, Vol. 266, no 1, p. 40-47Article in journal (Refereed) Published
    Abstract [en]

    Human serum albumin was adsorbed into porous silicon layers with thickness up to 3 µm and with different mean pore radius in the range 4.5-10 nm. The adsorbed amount of protein was quantified by I125 radioactive labeling techniques and ellipsometry. The results show that albumin penetrated into the pores when the mean pore radius was larger than 5.5 nm, but could not totally occupy the available surface area when the layer thickness was larger than 1 µm. Loading of albumin both into porous layers and onto plane silicon as a function of albumin concentration was also investigated. These measurements show that loading of protein increased with protein concentration at least up to 10 mg/ml for porous silicon and up to 1 mg/ml for plane silicon. The maximum deposition into the type of porous layers used here was 28 µg/cm2, compared to 0.36 µg/cm2 for plane silicon. © 2003 Elsevier Inc. All rights reserved.

    Keywords
    Ellipsometry, Human serum albumin, Porous silicon, Protein adsorption, Protein loading, Protein penetration
    National Category
    Engineering and Technology
    Identifiers
    urn:nbn:se:liu:diva-46472 (URN)10.1016/S0021-9797(03)00595-2 (DOI)
    Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2021-09-17
  • 49.
    Kiflemariam, Jordanos
    Linköping University, Department of Science and Technology.
    A Biomimetic Manganese Model for Artificial Photosynthesis: Q-band Electron Paramagnetic Resonance Study of a Novel Mn2(II,III) Complex2005Independent thesis Basic level (professional degree), 20 points / 30 hpStudent thesis
    Abstract [en]

    In natural oxygen-producing photosynthesis solar energy is stored as chemical energy, in carbohydrates, fats and amino acids, using water as electron source. The large transmembrane protein complex, PSII, is the key enzyme in the light-driven reactions. Water oxidation is accomplished by a triad in PSII in which the Mn-cluster plays an important role. In the artificial photosynthetic system, nature’s photosynthesis will be mimicked such that hydrogen, a sustainable energy source, can be produced from solar energy and water alone. Since water oxidiation requires the catalytic activity of a Mn-cluster in photosynthesis, different artificially constructed manganese complexes are investigated.

    The dinuclear ([Mn2(II,III)L(µ-OAc)2]ClO4), where L is the X-anion of 2-(N,N-Bis(2-methylpyridyl)aminomethyl)-6-(N-(3,5-ditert-butylbenzyl-2-hydroxy)-N-(pyridylmethyl)aminomethyl)-4-methylphenol, an unsymmetric ligand with two coordinating phenolate groups, has been studied. The two Mn-ions are linked via a mono-µ-oxo bridge and two acetate ligands. Q-band Electron Paramagnetic Resonance was conducted on the Unsymmetric Mn2(II,III) Complex. Aquired results show that the complex has a 2600 Gauss broad signal (11 400-14 000 Gauss) with 14-17 lines at g~2 and hyperfines of 120 Gauss. This is consistent with previous X-band studies. Q-band spectra of the Unsymmetric Mn(II,III) display increased hyperfine resolution compared to Qband spectra of the symmetric complex, Mn2(bpmp)(µ-OAC)2. This is noticeable since Unsymmetric Mn2(II,III) and Mn2 (bpmp)(µ-OAC)2 partly overlap in low-frequency experiments (X-band EPR).

    Further investigations are yet to be expected. Nevertheless, the conducted thesis study provides important knowledge in the futuristic goal of building an artificial super-complex.

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  • 50. Order onlineBuy this publication >>
    Klenkar, Goran
    Linköping University, Department of Physics, Chemistry and Biology, Sensor Science and Molecular Physics. Linköping University, The Institute of Technology.
    Protein Microarray Chips2007Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Life is a thing taken for granted by most. However, it is the life-long quest of many to unravel the mysteries of it. Understanding and characterizing the incomprehensively complex molecular interaction networks within a biological organism, which defines that organism, is a vital prerequisite to understand life itself. Already, there has been a lot of research conducted and a large knowledge has been obtained about these pathways over, especially, the last century. We have seen the fruits of these labors in e.g. the development of medicines which have been able to cure or at least arrest many diseases and conditions. However, many diseases are still incurable (e.g. cancer) and a lot more work is still needed for understanding them fully and designing successful treatments. This work describes a generic analytical tool platform for aiding in more efficient (bio)molecular interaction mapping analyses; protein microarray chips. Microarray chips are surfaces with micrometer sized features with the possibility of studying the interactions of many (thousands to tens of thousands) (bio)molecules in parallel. This allows for a higher throughput of analyses to be performed at a reduced time and cost. Protein microarrays have been around for approximately a decade, following in the footsteps of the, so far, more successfully used DNA microarrays (developed in the 1990s). Microarrays of proteins are more difficult to produce because of the more complex nature of proteins as compared to DNA. In our work we have constructed model surfaces which allow for the stable, highly oriented, and functional immobilization of proteins in an array format. Our capture molecules are based on multivalent units of the chelator nitrilotriacetic acid (NTA), which is able to bind histidine-tagged proteins. Furthermore, we have explored an approach for studying lipid membrane bound systems, e.g. receptor-ligand interactions, in a parallelized, microarray format. The approach relies on the addressable, DNA-mediated adsorption of tagged lipid vesicles. In an analogous work we have used the protein microarray concept for the detection of four common narcotics (heroin, amphetamine, ecstasy, and cocaine). The detection is based on the displacement of loosely bound antibodies from surface array positions upon injection of a specific target analyte, i.e. a narcotic substance. The proof-of-concept chip can easily be expanded to monitor many more narcotic substances. In addition, we have also been able to simultaneously detect the explosive trinitrotoluene (TNT) along with the narcotics, showing that the chip is a versatile platform for the detection of virtually any type of harmful or illegal compound. This type of biosensor system is potentially envisaged to be used in the fight against crime, terrorism, drug abuse etc. Infrared reflection absorption spectroscopy together with ellipsometry has been used to characterize molecular layers used in the fabrication processes of the microarray features. Imaging surface plasmon resonance operating in the ellipsometric mode is subsequently used for functional evaluation of the microarrays using a well-defined receptor-ligand model system. This approach allows simultaneous and continuous monitoring of binding events taking place in multiple regions of interest on the microarray chip. A common characteristic of all the instrumentation used is that there is no requirement for labeling of the biomolecules to be detected, e.g. with fluorescent or radioactive probes. This feature allows for a flexible assay design and the use of more native proteins, without any time-consuming pretreatments.

    List of papers
    1. Piezo Dispensed Microarray of Multivalent Chelating Thiols for Dissecting Complex Protein-Protein Interactions
    Open this publication in new window or tab >>Piezo Dispensed Microarray of Multivalent Chelating Thiols for Dissecting Complex Protein-Protein Interactions
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    2006 (English)In: Analytical Chemistry, ISSN 0003-2700, Vol. 78, no 11, p. 3643-3650Article in journal (Refereed) Published
    Abstract [en]

    The fabrication of a novel biochip, designed for dissection of multiprotein complex formation, is reported. An array of metal chelators has been produced by piezo dispensing of a bis-nitrilotriacetic acid (bis-NTA) thiol on evaporated gold thin films, prestructured with a microcontact printed grid of eicosanethiols. The bis-NTA thiol is mixed in various proportions with an inert, tri(ethylene glycol) hexadecane thiol, and the thickness and morphological homogeneity of the dispensed layers are characterized by imaging ellipsometry before and after back-filling with the same inert thiol and subsequent rinsing. It is found that the dispensed areas display a monotonic increase in thickness with increasing molar fraction of bis-NTA in the dispensing solution, and they are consistently a few Ångströms thicker than those prepared at the same molar fraction by solution self-assembly under equilibrium-like conditions. The bulkiness of the bis-NTA tail group and the short period of time available for chemisorption and in-plane organization of the dispensed thiols are most likely responsible for the observed difference in thickness. Moreover, the functional properties of this biochip are demonstrated by studying multiple protein−protein interactions using imaging surface plasmon resonance. The subunits of the type I interferon receptor are immobilized as a composition array determined by the surface concentration of bis-NTA in the array elements. Ligand dissociation kinetics depends on the receptor surface concentration, which is ascribed to the formation of a ternary complex by simultaneous interaction of the ligand with the two receptor subunits. Thus, multiplexed monitoring of binding phenomena at various compositions (receptor densities) offers a powerful tool to dissect protein−protein interactions.

    National Category
    Natural Sciences
    Identifiers
    urn:nbn:se:liu:diva-14515 (URN)10.1021/ac060024+ (DOI)
    Available from: 2007-05-22 Created: 2007-05-22 Last updated: 2009-05-22
    2. Differential Protein Assembly on Micropatterned Surfaces with Tailored Molecular and Surface Multivalency
    Open this publication in new window or tab >>Differential Protein Assembly on Micropatterned Surfaces with Tailored Molecular and Surface Multivalency
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    2006 (English)In: ChemBioChem, ISSN 1439-4227, Vol. 7, no 9, p. 1325-1329Article in journal (Refereed) Published
    Keywords
    arrays, multivalent interactions, nitrilotriacetic acid, protein-protein interactions, surface plasmon resonance
    National Category
    Natural Sciences
    Identifiers
    urn:nbn:se:liu:diva-14516 (URN)10.1002/cbic.200600176 (DOI)
    Available from: 2007-05-22 Created: 2007-05-22 Last updated: 2009-06-08
    3. Multivalent Self-Assembled Monolayers with Terminal Mono-, Bis-, and Tris-nitrilotriacetic Acid Groups: Characterization and Application
    Open this publication in new window or tab >>Multivalent Self-Assembled Monolayers with Terminal Mono-, Bis-, and Tris-nitrilotriacetic Acid Groups: Characterization and Application
    Show others...
    Manuscript (Other academic)
    Identifiers
    urn:nbn:se:liu:diva-14517 (URN)
    Available from: 2007-05-22 Created: 2007-05-22 Last updated: 2010-01-13
    4. A Microarray for Addressable Adsorption of Lipid Vesicles and Subsequent Protein Interaction Studies
    Open this publication in new window or tab >>A Microarray for Addressable Adsorption of Lipid Vesicles and Subsequent Protein Interaction Studies
    Show others...
    Manuscript (Other academic)
    Identifiers
    urn:nbn:se:liu:diva-14518 (URN)
    Available from: 2007-05-22 Created: 2007-05-22 Last updated: 2010-01-13
    5. A Microarray Chip for Label-Free Detection of Narcotics
    Open this publication in new window or tab >>A Microarray Chip for Label-Free Detection of Narcotics
    2008 (English)In: Analytical and Bioanalytical Chemistry, ISSN 1618-2642, E-ISSN 1618-2650, Vol. 391, no 5, p. 1679-1688Article in journal (Refereed) Published
    Abstract [en]

    A protein array chip for label-free optical detection of low molecular weight compounds has been developed. As a proof of principle, the chip is proven capable of rapidly (approximately 1 min) determining hits from aqueous cocktails composed of four common narcotics, cocaine, ecstasy, heroin, and amphetamine, using imaging surface plasmon resonance (SPR) as the detection principle. The chip is produced by injecting a mixture of antibodies and letting them self-sort and bind to narcotic analog coupled proteins already present in a predefined pattern on the supporting substrate. An indirect detection method, where antibodies are displaced from the surface upon recognition of their corresponding narcotics, is used to obtain the optical contrast and thus a detectable SPR and/or ellipsometric signal. Two types of readouts are possible from the present setup: intensity SPR images and SPR/ellipsometric sensorgrams. Positive hits were routinely obtained for analyte concentrations of 50 pg/μL and the limit of detection, without any parameter optimizations, seems to fall in the range 0.5 pg/μL (1.4 nM) for heroin, 2.5 pg/μL (8.2 nM) for cocaine, and 5 pg/μL for the other two narcotics (26 nM for ecstasy and 37 nM for amphetamine). With improved readout possibilities (sampling frequency), signal evaluation algorithms, and antibody–antigen design strategies, we believe this limit can be further improved. The chip is shown to work for many measurement cycles with excellent reproducibility. Moreover, with a more advanced fluidic system, excess injected antibodies could be collected and reused for many cycles, which could make the running costs of the system very low. The chip is in no way limited to detection of narcotics. Other low molecular weight compounds could easily be detected on the same chip. For example, trinitrotoluene detection has already been demonstrated using our chip. Possible areas of application for the system are therefore envisaged in airport and underground transport security, customs, drug interdiction, forensics, and as warning alerts on military equipment and personnel.

    Keywords
    Protein microarray, Imaging surface plasmon resonance, Imaging ellipsometry, Narcotics trace detection, Biosensors, Antibody displacement
    National Category
    Natural Sciences
    Identifiers
    urn:nbn:se:liu:diva-14519 (URN)10.1007/s00216-008-1839-9 (DOI)
    Available from: 2007-05-22 Created: 2007-05-22 Last updated: 2017-12-13
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