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  • 51.
    Jonson, Maria
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelning för neurobiologi. Linköpings universitet, Medicinska fakulteten.
    Nyström, Sofie
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Sandberg, Alexander
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Carlback, Marcus
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten.
    Michno, Wojciech
    Univ Gothenburg, Sweden.
    Hanrieder, Jorg
    Univ Gothenburg, Sweden; UCL, England.
    Starkenberg, Annika
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten.
    Peter, K.
    Nilsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Thor, Stefan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för hematopoes och utvecklingsbiologi. Linköpings universitet, Medicinska fakulteten.
    Hammarström, Per
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Amyloid fibril polymorphism and cell-specific toxicity in vivo2019Inngår i: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 26, nr sup1, s. 136-137Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    n/a

  • 52.
    Jonsson, Maria
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Nyström, Sofie
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Sandberg, Alexander
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Carlback, Marcus
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Michno, Wojciech
    Univ Gothenburg, Sweden.
    Hanrieder, Jorg
    Univ Gothenburg, Sweden; UCL, England.
    Starkenberg, Annika
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Nilsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Thor, Stefan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Hammarström, Per
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Aggregated A beta 1-42 Is Selectively Toxic for Neurons, Whereas Glial Cells Produce Mature Fibrils with Low Toxicity in Drosophila2018Inngår i: Cell Chemical Biology, ISSN 2451-9456, E-ISSN 2451-9448, Vol. 25, nr 5, s. 595-610Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The basis for selective vulnerability of certain cell types for misfolded proteins (MPs) in neurodegenerative diseases is largely unknown. This knowledge is crucial for understanding disease progression in relation to MPs spreading in the CNS. We assessed this issue in Drosophila by cell-specific expression of human A beta 1-42 associated with Alzheimers disease. Expression of A beta 1-42 in various neurons resulted in concentration-dependent severe neurodegenerative phenotypes, and intraneuronal ringtangle-like aggregates with immature fibril properties when analyzed by aggregate-specific ligands. Unexpectedly, expression of A beta 1-42 from a pan-glial driver produced a mild phenotype despite massive brain load of A beta 1-42 aggregates, even higher than in the strongest neuronal driver. Glial cells formed more mature fibrous aggregates, morphologically distinct from aggregates found in neurons, and was mainly extracellular. Our findings implicate that A beta 1-42 cytotoxicity is both cell and aggregate morphotype dependent.

  • 53.
    Karlsson, Fredrik
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biomolekylär och Organisk Elektronik. Linköpings universitet, Tekniska högskolan.
    Åsberg, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biomolekylär och Organisk Elektronik. Linköpings universitet, Tekniska högskolan.
    Nilsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biomolekylär och Organisk Elektronik. Linköpings universitet, Tekniska högskolan.
    Inganäs, Olle
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biomolekylär och Organisk Elektronik. Linköpings universitet, Tekniska högskolan.
    Interactions between a zwitterionic polythiophene derivative and oligonucleotides as resolved by fluorescence resonance energy transfer2005Inngår i: Chemistry of Materials, ISSN 0897-4756, E-ISSN 1520-5002, Vol. 17, nr 16, s. 4204-4211Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The interactions between a zwitterionic polythiophene derivative, POWT, and DNA oligonucleotides in solution have been studied by FRET (fluorescence resonance energy transfer). When POWT and ssDNA are bound alone in a complex, the distance between them is at its smallest. The distance increases when adding complementary DNA, but POWT is still mainly bound to the first DNA strand. We find that two POWT chains bind to one DNA strand, and the two POWT chains seem held together in pairs, unable to separate, as they can only bind to and quench half their own amount of labeled DNA. This POWT−POWT complex appears to dissociate at lower concentrations. ssDNA attached to POWT in a complex can also be substituted by other ssDNA in solution; this occurs to 50% when the free DNA is present in 10-fold concentration compared to the ssDNA bound to POWT. Titration studies at different concentrations show positive cooperativity in the binding of POWT and ssDNA into a complex. The hybridization of complementary DNA to the same complex involves no cooperativity. These observations indicate interesting possibilities for the use of POWT as a DNA sensor.

  • 54.
    Khodaparast, Ladan
    et al.
    SWITCH Lab, Belgium; KULeuven, Belgium.
    Khodaparast, Laleh
    SWITCH Lab, Belgium; KULeuven, Belgium.
    Gallardo, Rodrigo
    SWITCH Lab, Belgium; KULeuven, Belgium.
    Louros, Nikolaos N.
    SWITCH Lab, Belgium; KULeuven, Belgium.
    Michiels, Emiel
    SWITCH Lab, Belgium; KULeuven, Belgium.
    Ramakrishnan, Reshmi
    SWITCH Lab, Belgium; KULeuven, Belgium.
    Ramakers, Meine
    SWITCH Lab, Belgium; KULeuven, Belgium.
    Claes, Filip
    SWITCH Lab, Belgium; KULeuven, Belgium.
    Young, Lydia
    Univ Leeds, England; Univ Leeds, England.
    Shahrooei, Mohammad
    KULeuven, Belgium.
    Wilkinson, Hannah
    SWITCH Lab, Belgium; KULeuven, Belgium.
    Desager, Matyas
    SWITCH Lab, Belgium; KULeuven, Belgium.
    Tadesse, Wubishet Mengistu
    KULeuven, Belgium.
    Nilsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Hammarström, Per
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Aertsen, Abram
    KULeuven, Belgium.
    Carpentier, Sebastien
    KULeuven, Belgium.
    Van Eldere, Johan
    KULeuven, Belgium.
    Rousseau, Frederic
    SWITCH Lab, Belgium; KULeuven, Belgium.
    Schymkowitz, Joost
    SWITCH Lab, Belgium; KULeuven, Belgium.
    Aggregating sequences that occur in many proteins constitute weak spots of bacterial proteostasis2018Inngår i: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 9, artikkel-id 866Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aggregation is a sequence-specific process, nucleated by short aggregation-prone regions (APRs) that can be exploited to induce aggregation of proteins containing the same APR. Here, we find that most APRs are unique within a proteome, but that a small minority of APRs occur in many proteins. When aggregation is nucleated in bacteria by such frequently occurring APRs, it leads to massive and lethal inclusion body formation containing a large number of proteins. Buildup of bacterial resistance against these peptides is slow. In addition, the approach is effective against drug-resistant clinical isolates of Escherichia coli and Acinetobacter baumannii, reducing bacterial load in a murine bladder infection model. Our results indicate that redundant APRs are weak points of bacterial protein homeostasis and that targeting these may be an attractive antibacterial strategy.

  • 55.
    Klingstedt, Therése
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    Blechschmidt, Cristiane
    Charite, Germany .
    Nogalska, Anna
    University of So Calif, CA USA .
    Prokop, Stefan
    Charite, Germany .
    Häggqvist, Bo
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Molekylär och immunologisk patologi. Linköpings universitet, Hälsouniversitetet.
    Danielsson, Olof
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    King Engel, W
    University of So Calif, CA USA .
    Askanas, Valerie
    University of So Calif, CA USA .
    Heppner, Frank L.
    Charite, Germany .
    Nilsson, K Peter R
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    Luminescent Conjugated Oligothiophenes for Sensitive Fluorescent Assignment of Protein Inclusion Bodies2013Inngår i: ChemBioChem (Print), ISSN 1439-4227, E-ISSN 1439-7633, Vol. 14, nr 5, s. 607-616Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Small hydrophobic ligands identifying intracellular protein deposits are of great interest, as protein inclusion bodies are the pathological hallmark of several degenerative diseases. Here we report that fluorescent amyloid ligands, termed luminescent conjugated oligothiophenes (LCOs), rapidly and with high sensitivity detect protein inclusion bodies in skeletal muscle tissue from patients with sporadic inclusion body myositis (s-IBM). LCOs having a conjugated backbone of at least five thiophene units emitted strong fluorescence upon binding, and showed co-localization with proteins reported to accumulate in s-IBM protein inclusion bodies. Compared with conventional amyloid ligands, LCOs identified a larger fraction of immunopositive inclusion bodies. When the conjugated thiophene backbone was extended with terminal carboxyl groups, the LCO revealed striking spectral differences between distinct protein inclusion bodies. We conclude that 1) LCOs are sensitive, rapid and powerful tools for identifying protein inclusion bodies and 2) LCOs identify a wider range of protein inclusion bodies than conventional amyloid ligands.

  • 56.
    Klingstedt, Therése
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    Kostareva, A
    Almazov Federal Centre of Heart, Blood and Endocrinology, St. Petersburg, Russian Federation.
    Sjöberg, G.
    Karolinska Institute, Stockholm, Sweden.
    Gudkova, A
    Almazov Federal Centre of Heart, Blood and Endocrinology, St. Petersburg, Russian Federation.
    Nilsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    Hammarström, Per
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biokemi. Linköpings universitet, Tekniska högskolan.
    Sejersen, T
    Karolinska Institute, Stockholm, Sweden.
    Desmin L345P transgenic mice exhibit morphological and biochemical features of amyloidosis of two distinct types2010Inngår i: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 31, nr Suppl. 1, s. 924-925Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    Background: Being a chief intermediate filament of the muscle tissue, desmin isimplicated in the sarcomeric organization, organelle positioning and mitochondrialfunction. Various desmin mutations have been reported as a possible cause forcardiomyopathies. Several reports on transgenic mice expressing mutant desminshowed deleterious effects of mutant desmin incorporated into filaments on cardiomyocyte function, but most importantly that accumulation of unfolded proteinaggregates plays an important pathogenic role in development of desminassociatedcardiomyopathies. Thus, in desmin transgenic mice with the L345Pmutation, which interferes in a dominant-negative manner with desmin polymerization,the accumulation of intracellular and extracellular amyloidogenic proteinaggregates was shown to be the key feature along with alteration of mitochondrialstructure and function. Therefore, the aim of this study was to characterizethe nature of amyloidogenic protein aggregates in L345P desmin transgenic miceon molecular and protein level.

    Material and methods: L345P desmin transgenic mice (DM) and WT mice 40weeks old were analyzed. Myocardial cryostat 10 micron sections were stainedwith conventional techniques (hematoxilin-eosin, Congo Red). A detailed amyloidcharacterization was carried out using novel optical probes called luminescentconjugated oligothiophenes and polythiophenes (LCOs and LCPs) that specificallystain various protein aggregates and give rise to conformation dependentemission spectra.

    Results: The most prominent feature of DM mice myocardium was misfoldedprotein depositions in perivascular space and between muscle fibers. Analysisof samples from DM mouse stained with LCO or LCP revealed the presence ofaggregates emitting light with two different emission spectra. Since the spectralproperties of the LCOs or LCPs are dependent on their conformation, the appearanceof two dissimilar emission spectra indicates that the probes might bindto two different types of amyloid aggregates within the tissue. Interestingly, aggregateswith emission spectra similar to one of the two types found in the DMmouse could also be found in WT mice, but in a much lower extent, suggesting asporadic cardiac amyloid pathology in C57 Bl/6 mice at 40 weeks, probably, as anative aging attribute.

    Conclusions: The L345P desmin mutation causes focal amyloid protein depositionin heart muscle of two distinct types. White first one can be a natural attributeof C57 Bl/6 mice detected with age, another one can be specifically responsiblefor the development of desmin-related cardiomyopathy.

  • 57.
    Klingstedt, Therése
    et al.
    Linköpings universitet, Tekniska högskolan. Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi.
    Nilsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    Conjugated polymers for enhanced bioimaging2011Inngår i: BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, ISSN 0304-4165, Vol. 1810, nr 3, s. 286-296Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Background: Conjugated polymers (CPs) have been used for creating bioimaging tools or biosensors that provide a direct link between spectral signal and different biological processes. The detection schemes of these sensors are mainly employing the efficient light harvesting properties or the conformation sensitive optical properties of the CPs. Hence, the presence of biomolecules or biological events can be detected through fluorescence resonance energy transfer (FRET) between the CP and an acceptor molecule, or through their impact on the conformation of the conjugated backbone, which is seen as an alteration of the optical properties of the CP. Scope of the review: In this review, the utilization of CPs for sensitive detection of DNA and protein conformational changes will be presented. The main part will be focused on the specific binding of CPs to protein deposits associated with protein misfolding diseases, such as Alzheimers disease (AD), and the discovery that tailor-made CPs can be used for in vivo optical imaging of protein aggregates will be discussed. Major conclusions: The unique optical properties of CPs can be used as molecular tools for sensitive detection of genetic material and for characterization of the pathological hallmarks associated with protein misfolding disorders, such as AD. General significance: CPs are novel molecular tools that can be used for sensitive bioimaging of biological processes and these tools offer the possibility to study biological events in a complementary fashion to conventional techniques. This article is part of a Special Issue entitled Nanotechnologies - Emerging Applications in Biomedicine.

  • 58.
    Klingstedt, Therése
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biokemi. Linköpings universitet, Tekniska högskolan.
    Nilsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    Luminescent conjugated poly- and oligo-thiophenes: optical ligands for spectral assignment of a plethora of protein aggregates2012Inngår i: Biochemical Society Transactions, ISSN 0300-5127, E-ISSN 1470-8752, Vol. 40, s. 704-710Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The deposition of protein aggregates in various parts of our body gives rise to several devastating diseases, and the development of probes for the selective detection of aggregated proteins is crucial to advance our understanding of the pathogenesis underlying these diseases. LCPs (luminescent conjugated polythiophenes) are fluorescent probes that bind selectively to protein aggregates. The conjugated thiophene backbone is flexible and offers a connection between the conformation and the emission properties, hence binding of LCPs gives the molecule a spectral fingerprint. The present review covers the utilization of LCPs to study the heterogeneity of protein aggregates. It emphasizes specifically the introduction of well-defined probes called LCOs (luminescent conjugated oligothiophenes) and reports how these molecules can be used for real-time in vivo imaging of cerebral plaques as well as for spectral discrimination of protein aggregates and detection of early species in the fibrillation pathway of amyloid beta-peptide.

  • 59.
    Klingstedt, Therése
    et al.
    Linköpings universitet, Tekniska fakulteten. Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi.
    Shirani, Hamid
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Mahler, Jasmin
    University of Tubingen, Germany; German Centre Neurodegenerat Disease, Germany.
    Wegenast-Braun, Bettina M.
    University of Tubingen, Germany; German Centre Neurodegenerat Disease, Germany.
    Nyström, Sofie
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Goedert, Michel
    MRC, England.
    Jucker, Mathias
    University of Tubingen, Germany; German Centre Neurodegenerat Disease, Germany.
    Nilsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Distinct Spacing Between Anionic Groups: An Essential Chemical Determinant for Achieving Thiophene-Based Ligands to Distinguish Beta-Amyloid or Tau Polymorphic Aggregates2015Inngår i: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 21, nr 25, s. 9072-9082Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The accumulation of protein aggregates is associated with many devastating neurodegenerative diseases and the existence of distinct aggregated morphotypes has been suggested to explain the heterogeneous phenotype reported for these diseases. Thus, the development of molecular probes able to distinguish such morphotypes is essential. We report an anionic tetrameric oligothiophene compound that can be utilized for spectral assignment of different morphotypes of -amyloid or tau aggregates present in transgenic mice at distinct ages. The ability of the ligand to spectrally distinguish between the aggregated morphotypes was reduced when the spacing between the anionic substituents along the conjugated thiophene backbone was altered, which verified that specific molecular interactions between the ligand and the protein aggregate are necessary to detect aggregate polymorphism. Our findings provide the structural and functional basis for the development of new fluorescent ligands that can distinguish between different morphotypes of protein aggregates.

  • 60.
    Klingstedt, Therése
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Shirani, Hamid
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Åslund, Andreas
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Cairns, Nigel J.
    Washington University, MO USA .
    Sigurdson, Christina J.
    University of Calif San Diego, CA USA .
    Goedert, Michel
    MRC, England .
    Nilsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    The Structural Basis for Optimal Performance of Oligothiophene-Based Fluorescent Amyloid Ligands: Conformational Flexibility is Essential for Spectral Assignment of a Diversity of Protein Aggregates2013Inngår i: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 19, nr 31, s. 10179-10192Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Protein misfolding diseases are characterized by deposition of protein aggregates, and optical ligands for molecular characterization of these disease-associated structures are important for understanding their potential role in the pathogenesis of the disease. Luminescent conjugated oligothiophenes (LCOs) have proven useful for optical identification of a broader subset of disease-associated protein aggregates than conventional ligands, such as thioflavin T and Congo red. Herein, the molecular requirements for achieving LCOs able to detect nonthioflavinophilic Aβ aggregates or non-congophilic prion aggregates, as well as spectrally discriminate Aβ and tau aggregates, were investigated. An anionic pentameric LCO was subjected to chemical engineering by: 1) replacing thiophene units with selenophene or phenylene moieties, or 2) alternating the anionic substituents along the thiophene backbone. In addition, two asymmetric tetrameric ligands were generated. Overall, the results from this study identified conformational freedom and extended conjugation of the conjugated backbone as crucial determinants for obtaining superior thiophene-based optical ligands for sensitive detection and spectral assignment of disease-associated protein aggregates.

  • 61.
    Klingstedt, Therése
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Shirani, Hamid
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Åslund, K. O. Andreas
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Cairns, Nigel J.
    Department of Neurology, Alzheimer’s Disease Research Center, Washington University St. Louis, United States.
    Sigurdson, Christina J.
    Department of Pathology, University of California, San Diego, La Jolla, California, United States.
    Goedert, Michel
    MRC Laboratory of Molecular Biology Hills Road, Cambridge, UK.
    Nilsson, K. Peter R.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    The structural basis for optimal performance of oligothiophene based fluorescent amyloid ligands: Conformational flexibility is essential for spectral assignment of a diversity of protein aggregatesManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Protein misfolding diseases are characterized by deposition of protein aggregates and optical ligands for molecular characterization of these disease-associated structures are important for understanding their potential role in the pathogenesis of the disease. Luminescent conjugated oligothiophenes (LCOs) have proven useful for optical identification of a broader subset of disease-associated protein aggregates than conventional ligands, such as Thioflavin T (ThT) and Congo red. Herein, the molecular requirements for achieving LCOs able to detect non-thioflavinophilic Aβ aggregates or non-congophilic prion aggregates, as well as spectrally discriminate Aβ and tau aggregates, were investigated. An anionic pentameric LCO was subjected to chemical engineering by i) replacing thiophene units with selenophene or phenylene moieties or ii) alternating the anionic substituents along the  thiophene backbone. In addition, two asymmetric tetrameric ligands were  generated. Overall, the results from this study identified conformational  freedom and extended conjugation of the conjugated backbone as crucial  determinants for obtaining superior thiophene-based optical ligands for  sensitive detection and spectral assignment of diseaseassociated protein aggregates.

  • 62.
    Klingstedt, Therése
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    Åslund, Andreas
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    Simon, Rozalyn
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    Johansson, Leif B. G.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    Mason, Jeffrey
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    Nyström, Sofie
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Proteinkemi. Linköpings universitet, Tekniska högskolan.
    Hammarström, Per
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Proteinkemi. Linköpings universitet, Tekniska högskolan.
    Nilsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    Synthesis of a library of oligothiophenes and their utilization as fluorescent ligands for spectral assignment of protein aggregates2011Inngår i: Organic and biomolecular chemistry, ISSN 1477-0520, E-ISSN 1477-0539, Vol. 9, nr 24, s. 8356-8370Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Molecular probes for selective identification of protein aggregates are important to advance our understanding of the molecular pathogenesis underlying protein aggregation diseases. Here we report the chemical design of a library of anionic luminescent conjugated oligothiophenes (LCOs), which can be utilized as ligands for detection of protein aggregates. Certain molecular requirements were shown to be necessary for detecting (i) early non-thioflavinophilic protein assemblies of A beta 1-42 and insulin preceding the formation of amyloid fibrils and (ii) for obtaining distinct spectral signatures of the two main pathological hallmarks observed in human Alzheimers diease brain tissue (A beta plaques and neurofibrillary tangles). Our findings suggest that a superior anionic LCO-based ligand should have a backbone consisting of five to seven thiophene units and carboxyl groups extending the conjugated thiophene backbone. Such LCOs will be highly useful for studying the underlying molecular events of protein aggregation diseases and could also be utilized for the development of novel diagnostic tools for these diseases.

  • 63.
    LeVine III, Harry
    et al.
    University of Kentucky, Lexington, USA.
    Nilsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Hammarström, Per
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Reporters of amyloid structural polymorphism2014Inngår i: Bio-nanoimaging: protein misfolding & aggregation / [ed] Vladimir N. Uversky, Yuri L. Lyubchenko, London: Academic Press, 2014, s. 69-79Kapittel i bok, del av antologi (Annet vitenskapelig)
    Abstract [en]

    Misfolding of proteins induced by environmental conditions or by the presence of destabilizing mutations often triggers squestration (aggresome formation) or cellular removal (unfolded protein response (UPR), autophagy) intracellular responses. Extracellular aggregates are phagocytosed or endocytosed by macrophages in the periphery and microglia and astrocytes in the brain and central nervous system. In some cases a highly stable altemative assembly structure, an amyloid fibril, is formed that is highly resistant to degadation and thus accumulates.

  • 64.
    Lindgren, M.
    et al.
    Department of Physics, Norwegian University of Science and Technology, 7491 Trondheim, Norway.
    Glimsdal, E.
    Department of Physics, Norwegian University of Science and Technology, 7491 Trondheim, Norway.
    Åslund, Andreas
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    Simon, Rozalyn
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska fakulteten.
    Hammarström, Per
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biokemi. Linköpings universitet, Tekniska högskolan.
    Nilsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    Luminescence and two-photon absorption cross section of novel oligomeric luminescent conjugated polythiophenes for diagnostics of amyloid fibrils2010Inngår i: Nonlinear Optics Quantum Optics, ISSN 1543-0537, Vol. 40, nr 1-4, s. 241-251Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Here we present the TPA cross section and quantum efficiencies of a series of novel oligomeric luminescent conjugated polythiophenes used for detection and spectral diagnostics of amyloid protein aggregates of the amyloid-beta peptide associated with Alzheimers disease. Specifically, these probes consist of pentameric or heptameric thiophenes derivatives with carboxylic substituents attached onto various thiophene rings. The probes absorbs over a broad range approx. 400-500 nm with quantum efficiency of approx. 20% in at neutral pH conditions, and also showed TPA cross sections of 5-50 GM in the range 700-840 nm, in the same order of magnitude as commonly used fluorescein derivatives. Importantly, the multiphoton excitation capabilities of LCPs provided excellent performance when compared to imaging using conventional "single photon" excitation. It is also demonstrated their utilization in both one-and two-photon excitation laser scanning microscope spectral imaging for diagnostics of Alzheimer disease pathology in ex vivo histological sections.

  • 65.
    Lindgren, Mikael
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi. Linköpings universitet, Tekniska högskolan.
    Stabo-Eeg, Frantz
    Norwegian University of Science and Technology.
    Nilsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biomolekylär och Organisk Elektronik. Linköpings universitet, Tekniska högskolan.
    Hammarström, Per
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biokemi. Linköpings universitet, Tekniska högskolan.
    Inganäs, Olle
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biomolekylär och Organisk Elektronik. Linköpings universitet, Tekniska högskolan.
    Biosensing and -imaging with enantiomeric luminescent conjugated polythiophenes using single - and multiphoton excitation2006Inngår i: Proceedings of International Symposium on Biophotonics, Nanophotonics and Metamaterials, IEEE , 2006, s. 226-226Konferansepaper (Fagfellevurdert)
  • 66.
    Loffler, S.
    et al.
    Karolinska Institute, Sweden.
    Melican, K.
    Karolinska Institute, Sweden.
    Nilsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Richter-Dahlfors, A.
    Karolinska Institute, Sweden.
    Organic bioelectronics in medicine2017Inngår i: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 282, nr 1, s. 24-36Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A major challenge in the growing field of bioelectronic medicine is the development of tissue interface technologies promoting device integration with biological tissues. Materials based on organic bioelectronics show great promise due to a unique combination of electronic and ionic conductivity properties. In this review, we outline exciting developments in the field of organic bioelectronics and demonstrate the medical importance of these active, electronically controllable materials. Importantly, organic bioelectronics offer a means to control cell-surface attachment as required for many device-tissue applications. Experiments have shown that cells readily attach and proliferate on reduced but not oxidized organic bioelectronic materials. In another application, the active properties of organic bioelectronics were used to develop electronically triggered systems for drug release. After incorporating drugs by advanced loading strategies, small compound drugs were released upon electrochemical trigger, independent of charge. Another type of delivery device was used to achieve well-controlled, spatiotemporal delivery of cationic drugs. Via electrophoretic transport within a polymer, cations were delivered with single-cell precision. Finally, organic bioelectronic materials are commonly used as electrode coatings improving the electrical properties of recording and stimulation electrodes. Because such coatings drastically reduce the electrode impedance, smaller electrodes with improved signal-to-noise ratio can be fabricated. Thus, rapid technological advancement combined with the creation of tiny electronic devices reacting to changes in the tissue environment helps to promote the transition from standard pharmaceutical therapy to treatment based on electroceuticals. Moreover, the widening repertoire of organic bioelectronics will expand the options for true biological interfaces, providing the basis for personalized bioelectronic medicine.

  • 67.
    Loffler, Susanne
    et al.
    Karolinska Inst, Sweden.
    Antypas, Hails
    Karolinska Inst, Sweden.
    Choong, Ferdinand X.
    Karolinska Inst, Sweden.
    Nilsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Richter-Dahlfors, Agneta
    Karolinska Inst, Sweden.
    Conjugated Oligo- and Polymers for Bacterial Sensing2019Inngår i: Frontiers in Chemistry, E-ISSN 2296-2646, Vol. 7, artikkel-id 265Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Fast and accurate detection of bacteria and differentiation between pathogenic and commensal colonization are important keys in preventing the emergence and spread of bacterial resistance toward antibiotics. As bacteria undergo major lifestyle changes during colonization, bacterial sensing needs to be achieved on different levels. In this review, we describe how conjugated oligo- and polymers are used to detect bacterial colonization. We summarize how oligothiophene derivatives have been tailor-made for detection of biopolymers produced by a wide range of bacteria upon entering the biofilm lifestyle. We further describe how these findings are translated into diagnostic approaches for biofilm-related infections. Collectively, this provides an overview on how synthetic biorecognition elements can be used to produce fast and easy diagnostic tools and new methods for infection control.

  • 68.
    Lord, Anna
    et al.
    Uppsala University.
    Philipson, Ola
    Uppsala University.
    Klingstedt, Therése
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    Westermark, Gunilla
    Uppsala University.
    Hammarström, Per
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Proteinkemi. Linköpings universitet, Tekniska högskolan.
    Nilsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    Nilsson, Lars N. G.
    Observations in APP Bitransgenic Mice Suggest thatDiffuse and Compact Plaques Form via IndependentProcesses in Alzheimer’s Disease2011Inngår i: American Journal of Pathology, ISSN 0002-9440, E-ISSN 1525-2191, Vol. 178, nr 5, s. 2286-2298Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Studies of familial Alzheimer's disease suggest that misfolding and aggregation of amyloid-β (Aβ) peptides initiate the pathogenesis. The Arctic mutation of Aβ precursor protein (APP) results in AD, and Arctic Aβ is more prone to form Aβ protofibrils and extracellular deposits. Herein is demonstrated that the burden of diffuse Aβ deposits but not compact plaques is increased when tg-Swe mice are crossed with tg-ArcSwe mice synthesizing low levels of Arctic Aβ. The diffuse deposits in bitransgenic mice, which contain primarily wild-type Aβ42, accumulate in regions both with and without transgene expression. However, APP processing, when compared with tg-Swe, remains unchanged in young bitransgenic mice, whereas wild-type Aβ42 aggregation is accelerated and fibril architecture is altered in vitro and in vivo when a low level of Arctic Aβ42 is introduced. Thus, the increased number of diffuse deposits is likely due to physical interactions between Arctic Aβ and wild-type Aβ42. The selective increase of a single type of parenchymal Aβ deposit suggests that different pathways lead to formation of diffuse and compact plaques. These findings could have general implications for Alzheimer's disease pathogenesis and particular relevance to patients heterozygous for the Arctic APP mutation. Moreover, it further illustrates how Aβ neuropathologic features can be manipulated in vivo by mechanisms similar to those originally conceptualized in prion research.

  • 69.
    Magnusson, Karin
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Appelqvist, Hanna
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Cieslar-Pobuda, Artur
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet. Institute of Automatic Control, Silesian University of of TechnologyGliwice, Poland.
    Wigenius, Jens
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biomolekylär och Organisk Elektronik. Linköpings universitet, Tekniska högskolan. Carl Zeiss AB, Sweden.
    Karlsson, Thommie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet. Application Specialist Confocal Microscopy at Leica MicrosystemsIL, United States.
    Los, Marek Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet. Department of Pathology, Pomeranian Medical UniversitySzczecin, Poland.
    Kågedal, Bertil
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk kemi.
    Jonasson, Jon
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk patologi och klinisk genetik.
    Nilsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Differential vital staining of normal fibroblasts and melanoma cells by an anionic conjugated polyelectrolyte2015Inngår i: Cytometry Part A, ISSN 1552-4922, E-ISSN 1552-4930, Vol. 87, nr 3, s. 262-272Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Molecular probes for imaging of live cells are of great interest for studying biological and pathological processes. The anionic luminescent conjugated polythiophene (LCP) polythiophene acetic acid (PTAA), has previously been used for vital staining of cultured fibroblasts as well as transformed cells with results indicating differential staining due to cell phenotype. Herein, we investigated the behavior of PTAA in two normal and five transformed cells lines. PTAA fluorescence in normal cells appeared in a peripheral punctated pattern whereas the probe was more concentrated in a one-sided perinuclear localization in the five transformed cell lines. In fibroblasts, PTAA fluorescence was initially associated with fibronectin and after 24 h partially localized to lysosomes. The uptake and intracellular target in malignant melanoma cells was more ambiguous and the intracellular target of PTAA in melanoma cells is still elusive. PTAA was well tolerated by both fibroblasts and melanoma cells, and microscopic analysis as well as viability assays showed no signs of negative influence on growth. Stained cells maintained their proliferation rate for at least 12 generations. Although the probe itself was nontoxic, photoinduced cellular toxicity was observed in both cell lines upon irradiation directly after staining. However, no cytotoxicity was detected when the cells were irradiated 24 h after staining, indicating that the photoinduced toxicity is dependent on the cellular location of the probe. Overall, these studies certified PTAA as a useful agent for vital staining of cells, and that PTAA can potentially be used to study cancer-related biological and pathological processes.

  • 70.
    Magnusson, Karin
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Appelqvist, Hanna
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Cieślar-Pobuda, Artur
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Bäck, Marcus
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Kågedal, Bertil
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Jonasson, Jon
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk patologi och klinisk genetik.
    Los, Marek J.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Nilsson, Peter R.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    An imidazole functionalized pentameric thiophene displays different staining patterns in normal and malignant cells2015Inngår i: Frontiers in Chemistry, E-ISSN 2296-2646, Vol. 3, artikkel-id 58Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Molecular tools for fluorescent imaging of cells and their components are vital for understanding the function and activity of cells. Here, we report an imidazole functionalized pentameric oligothiophene, p-HTIm, that can be utilized for fluorescent imaging of cells. p-HTIm fluorescence in normal cells appeared in a peripheral punctate pattern partially co-localized with lysosomes, whereas a one-sided perinuclear Golgi associated localization of the dye was observed in malignant cells. The uptake of p-HTIm was temperature dependent and the intracellular target was reached within 1 h after staining. The ability of p-HTIm to stain cells was reduced when the imidazole side chain was chemically altered, verifying that specific imidazole side-chain functionalities are necessary for achieving the observed cellular staining. Our findings confirm that properly functionalized oligothiophenes can be utilized as fluorescent tools for vital staining of cells and that the selectivity towards distinct intracellular targets are highly dependent on the side-chain functionalities along the conjugated thiophene backbone.

  • 71.
    Magnusson, Karin
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Simon, Rozalyn
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biokemi. Linköpings universitet, Tekniska högskolan.
    Joshi-Barr, Shivanjali
    University of Calif San Diego.
    Sigurdson, Christina
    University of Calif San Diego.
    Nilsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    Conformation-sensitive probes for strain-specific characterization of prion aggregates in PRION, vol 6, issue , pp 47-472012Inngår i: PRION, Landes Bioscience , 2012, Vol. 6, s. 47-47Konferansepaper (Fagfellevurdert)
    Abstract [en]

    n/a

  • 72.
    Magnusson, Karin
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Simon, Rozalyn
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Sjölander, Daniel
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Sigurdson, Christina J.
    Department of Pathology, Unversity of California, San Diego, USA.
    Hammarström, Per
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Nilsson, Peter R
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Multimodal fluorescene microscopy of prion strain specific PrP deposits stained by thiophene-bassed amyloid ligands2014Inngår i: Prion, ISSN 1933-6896, E-ISSN 1933-690X, Vol. 8, nr 4, s. 319-329Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The disease-associated prion protein (PrP) forms aggregates which vary in structural conformation yet share identical primary sequence. These variations in PrP conformation are believed to manifest in prion strains exhibiting distinctly different periods of disease incubation as well as regionally specific aggregate deposition within the brain. The anionic luminescent conjugated polythiophene (LCP), polythiophene acetic acid (PTAA) has previously been used to distinguish PrP deposits associated with distinct mouse adapted strains via distinct fluorescence emission profiles from the dye. Here we employed PTAA and 3 structurally related chemically defined luminescent conjugated oligothiophenes (LCOs) to stain brain tissue sections from mice inoculated with 2 distinct prion strains. Our results showed that in addition to emission spectra, excitation, and fluorescence lifetime imaging microscopy (FLIM) can fruitfully be assessed for optical distinction of PrP deposits associated with distinct prion strains. Our findings support the theory that alterations in LCP/LCO fluorescence are due to distinct conformational restriction of the thiophene backbone upon interaction with PrP aggregates associated with distinct prion strains. We foresee that LCP and LCO staining in combination with multimodal fluorescence microscopy might aid in detecting structural differences among discrete protein aggregates and in linking protein conformational features with disease phenotypes for a variety of neurodegenerative proteinopathies.

  • 73.
    Mahajan, V S
    et al.
    Institute of Pathology, Medical University Graz, Graz, Austria.
    Klingstedt, Therése
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    Nilsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    Fuchsbichler, A
    Institute of Pathology, Medical University Graz, Graz, Austria.
    Kashofer, K
    Institute of Pathology, Medical University Graz, Graz, Austria.
    Abuja, P M
    Institute of Pathology, Medical University Graz, Graz, Austria.
    Denk, H
    Institute of Pathology, Medical University Graz, Graz, Austria.
    Zatloukal, K
    Institute of Pathology, Medical University Graz, Graz, Austria.
    STRUCTURAL CHARACTERISTICS OF MISFOLDED PROTEINS IN LIVER DISEASE: EVIDENCE FOR CROSS beta-SHEET CONFORMATION IN MALLORY-DENK BODIES BUT NOT IN OTHER HEPATOCYTIC AGGREGATES2010Inngår i: Journal of Hepatology, ISSN 0168-8278, E-ISSN 1600-0641, Vol. 52, nr Suppl. 1, s. S308-S308Artikkel i tidsskrift (Annet vitenskapelig)
  • 74.
    Mahajan, Vineet
    et al.
    Medical University of Graz.
    Klingstedt, Therése
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biokemi. Linköpings universitet, Tekniska högskolan.
    Simon, Rozalyn
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Nilsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    Thueringer, Andrea
    Medical University of Graz.
    Kashofer, Karl
    Medical University of Graz.
    Haybaeck, Johannes
    Medical University of Graz.
    Denk, Helmut
    Medical University of Graz.
    Abuja, Peter M
    Medical University of Graz.
    Zatloukal, Kurt
    Medical University of Graz.
    Cross beta-Sheet Conformation of Keratin 8 Is a Specific Feature of Mallory-Denk Bodies Compared With Other Hepatocyte Inclusions2011Inngår i: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 141, nr 3, s. 1080-U428Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND andamp; AIMS: Mallory-Denk bodies (MDBs) are cytoplasmic protein aggregates in hepatocytes in steato-hepatitis and other liver diseases. We investigated the molecular structure of keratin 8 (K8) and 18 (K18), sequestosome 1/p62, and ubiquitin, which are the major constituents of MDBs, to investigate their formation and role in disease pathogenesis. METHODS: Luminescent conjugated oligothiophenes (LCOs), h-HTAA, and p-FTAA are fluorescent amyloid ligands that specifically bind proteins with cross beta-sheet conformation. We used LCOs to investigate conformational changes in MDBs in situ in human and murine livers as well as in transfection studies. RESULTS: LCO analysis showed cross beta-sheet conformation in human MDBs from patients with alcoholic and nonalcoholic steatohepatitis or hepatocellular carcinoma, but not in intracellular hyaline bodies, alpha(1)-antitrypsin deficiency, or ground-glass inclusions. LCOs bound to MDBs induced by 3,5diethoxycarbonyl-1,4-dihydrocollidine feeding of mice at all developmental stages. CHO-K1 cells transfected with various combinations of SQSTM1/p62, ubi, and Krt8/Krt18 showed that K8 was more likely to have cross beta-sheet conformation than K18, whereas p62 never had cross beta-sheet conformation. The different conformational properties of K8 and K18 were also shown by circular dichroism analysis. CONCLUSIONS: K8 can undergo conformational changes from predominantly alpha-helical to cross beta-sheet, which would allow it to form MDBs. These findings might account for the observation that krt8(-/-) mice do not form MDBs, whereas its excess facilitates MDB formation. LCOs might be used in diagnosis of liver disorders; they can be applied to formalin-fixed, paraffin-embedded tissues to characterize protein aggregates in liver cells.

  • 75.
    Mahler, Jasmin
    et al.
    University of Tubingen, Germany; German Centre Neurodegenerat Disease, Germany; University of Tubingen, Germany.
    Morales-Corraliza, Jose
    Nathan S Kline Institute Psychiat Research, NY 10962 USA; NYU, NY USA.
    Stolz, Julia
    University of Tubingen, Germany; German Centre Neurodegenerat Disease, Germany; University of Tubingen, Germany.
    Skodras, Angelos
    University of Tubingen, Germany; German Centre Neurodegenerat Disease, Germany.
    Radde, Rebecca
    University of Tubingen, Germany.
    Duma, Carmen C.
    University of Tubingen, Germany.
    Eisele, Yvonne S.
    University of Tubingen, Germany; German Centre Neurodegenerat Disease, Germany.
    Mazzella, Matthew J.
    Nathan S Kline Institute Psychiat Research, NY 10962 USA.
    Wong, Harrison
    Nathan S Kline Institute Psychiat Research, NY 10962 USA.
    Klunk, William E.
    NYU, NY USA; University of Pittsburgh, PA USA; University of Pittsburgh, PA 15261 USA.
    Nilsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Staufenbiel, Matthias
    University of Tubingen, Germany; German Centre Neurodegenerat Disease, Germany.
    Mathews, Paul M.
    Nathan S Kline Institute Psychiat Research, NY 10962 USA; NYU, NY USA.
    Jucker, Mathias
    University of Tubingen, Germany; German Centre Neurodegenerat Disease, Germany.
    Wegenast-Braun, Bettina M.
    University of Tubingen, Germany; German Centre Neurodegenerat Disease, Germany.
    Endogenous murine A beta increases amyloid deposition in APP23 but not in APPPS1 transgenic mice2015Inngår i: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 36, nr 7, s. 2241-2247Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Endogenous murine amyloid-beta peptide (A beta) is expressed in most A beta precursor protein (APP) transgenic mouse models of Alzheimers disease but its contribution to beta-amyloidosis remains unclear. We demonstrate similar to 35% increased cerebral A beta load in APP23 transgenic mice compared with age-matched APP23 mice on an App-null background. No such difference was found for the much faster A beta-depositing APPPS1 transgenic mouse model between animals with or without the murine App gene. Nevertheless, both APP23 and APPPS1 mice codeposited murine A beta, and immunoelectron microscopy revealed a tight association of murine A beta with human A beta fibrils. Deposition of murine A beta was considerably less efficient compared with the deposition of human A beta indicating a lower amyloidogenic potential of murine A beta in vivo. The amyloid dyes Pittsburgh Compound-B and pentamer formyl thiophene acetic acid did not differentiate between amyloid deposits consisting of human A beta and deposits of mixed human-murine A beta. Our data demonstrate a differential effect of murine A beta on human A beta deposition in different APP transgenic mice. The mechanistically complex interaction of human and mouse A beta may affect pathogenesis of the models and should be considered when models are used for translational preclinical studies.

  • 76.
    Maji, Samir K
    et al.
    ETH.
    Perrin, Marilyn H
    Salk Institute of Biological Studies.
    Sawaya, Michael R
    University of California.
    Jessberger, Sebastian
    ETH.
    Vadodaria, Krishna
    ETH.
    Rissman, Robert A
    University of California .
    Singru, Praful S
    Tufts Medical Centre.
    Nilsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    Simon, Rozalyn
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Schubert, David
    Salk Institute of Biological Studies.
    Eisenberg, David
    University of California.
    Rivier, Jean
    Salk Institute of Biological Studies.
    Sawchenko, Paul
    Salk Institute of Biological Studies.
    Vale, Wylie
    Salk Institute of Biological Studies.
    Riek, Roland
    ETH.
    Functional Amyloids As Natural Storage of Peptide Hormones in Pituitary Secretory Granules2009Inngår i: SCIENCE, ISSN 0036-8075, Vol. 325, nr 5938, s. 328-332Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Amyloids are highly organized cross-beta-sheet-rich protein or peptide aggregates that are associated with pathological conditions including Alzheimers disease and type II diabetes. However, amyloids may also have a normal biological function, as demonstrated by fungal prions, which are involved in prion replication, and the amyloid protein Pmel17, which is involved in mammalian skin pigmentation. We found that peptide and protein hormones in secretory granules of the endocrine system are stored in an amyloid-like cross-beta-sheet-rich conformation. Thus, functional amyloids in the pituitary and other organs can contribute to normal cell and tissue physiology.

  • 77.
    Margalith, Ilan
    et al.
    University of Zurich Hospital, Switzerland .
    Suter, Carlo
    University of Zurich Hospital, Switzerland .
    Ballmer, Boris
    University of Zurich Hospital, Switzerland .
    Schwarz, Petra
    University of Zurich Hospital, Switzerland .
    Tiberi, Cinzia
    University of Zurich Hospital, Switzerland .
    Sonati, Tiziana
    University of Zurich Hospital, Switzerland .
    Falsig, Jeppe
    University of Zurich Hospital, Switzerland .
    Nyström, Sofie
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biokemi. Linköpings universitet, Tekniska högskolan.
    Hammarström, Per
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biokemi. Linköpings universitet, Tekniska högskolan.
    Åslund, Andreas
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    Nilsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Yam, Alice
    Novartis Diagnost, USA .
    Whitters, Eric
    Novartis Diagnost, USA .
    Hornemann, Simone
    University of Zurich Hospital, Switzerland .
    Aguzzi, Adriano
    University of Zurich Hospital, Switzerland .
    Polythiophenes Inhibit Prion Propagation by Stabilizing Prion Protein (PrP) Aggregates2012Inngår i: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 287, nr 23, s. 18872-18887Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Luminescent conjugated polymers (LCPs) interact with ordered protein aggregates and sensitively detect amyloids of many different proteins, suggesting that they may possess antiprion properties. Here, we show that a variety of anionic, cationic, and zwitterionic LCPs reduced the infectivity of prion-containing brain homogenates and of prion-infected cerebellar organotypic cultured slices and decreased the amount of scrapie isoform of PrPC (PrPSc) oligomers that could be captured in an avidity assay. Paradoxically, treatment enhanced the resistance of PrPSc to proteolysis, triggered the compaction, and enhanced the resistance to proteolysis of recombinant mouse PrP(23-231) fibers. These results suggest that LCPs act as antiprion agents by transitioning PrP aggregates into structures with reduced frangibility. Moreover, ELISA on cerebellar organotypic cultured slices and in vitro conversion assays with mouse PrP(23-231) indicated that poly(thiophene-3-acetic acid) may additionally interfere with the generation of PrPSc by stabilizing the conformation of PrPC or of a transition intermediate. Therefore, LCPs represent a novel class of antiprion agents whose mode of action appears to rely on hyperstabilization, rather than destabilization, of PrPSc deposits.

  • 78.
    Maria Psonka-Antonczyk, Katarzyna
    et al.
    Norwegian University of Science and Technology.
    Duboisset, Julien
    Norwegian University of Science and Technology.
    Torger Stokke, Bjorn
    Norwegian University of Science and Technology.
    Zako, Tamotsu
    Riken Institute Phys and Chemistry Research.
    Kobayashi, Takahiro
    Riken Institute Phys and Chemistry Research.
    Maeda, Mizuo
    Riken Institute Phys and Chemistry Research.
    Nyström, Sofie
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biokemi. Linköpings universitet, Tekniska högskolan.
    Mason, Jeffrey
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Proteinkemi. Linköpings universitet, Tekniska fakulteten.
    Hammarström, Per
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biokemi. Linköpings universitet, Tekniska högskolan.
    Nilsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    Lindgren, Mikael
    Norwegian University of Science and Technology.
    Nanoscopic and Photonic Ultrastructural Characterization of Two Distinct Insulin Amyloid States2012Inngår i: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, ISSN 1661-6596, Vol. 13, nr 2, s. 1461-1480Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Two different conformational isoforms or amyloid strains of insulin with different cytotoxic capacity have been described previously. Herein these filamentous and fibrillar amyloid states of insulin were investigated using biophysical and spectroscopic techniques in combination with luminescent conjugated oligothiophenes (LCO). This new class of fluorescent probes has a well defined molecular structure with a distinct number of thiophene units that can adopt different dihedral angles depending on its binding site to an amyloid structure. Based on data from surface charge, hydrophobicity, fluorescence spectroscopy and imaging, along with atomic force microscopy (AFM), we deduce the ultrastructure and fluorescent properties of LCO stained insulin fibrils and filaments. Combined total internal reflection fluorescence microscopy (TIRFM) and AFM revealed rigid linear fibrous assemblies of fibrils whereas filaments showed a short curvilinear morphology which assemble into cloudy deposits. All studied LCOs bound to the filaments afforded more blue-shifted excitation and emission spectra in contrast to those corresponding to the fibril indicating a different LCO binding site, which was also supported by less efficient hydrophobic probe binding. Taken together, the multi-tool approach used here indicates the power of ultrastructure identification applying AFM together with LCO fluorescence interrogation, including TIRFM, to resolve structural differences between amyloid states.

  • 79.
    Michno, Wojciech
    et al.
    Univ Gothenburg, Sweden.
    Kaya, Ibrahim
    Univ Gothenburg, Sweden.
    Nyström, Sofie
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Guerard, Laurent
    Univ Gothenburg, Sweden; Univ Basel, Switzerland.
    Nilsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Hammarström, Per
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Blennow, Kaj
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Zetterberg, Henrik
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden; UCL, England.
    Hanrieder, Jorg
    Univ Gothenburg, Sweden; UCL, England; Chalmers Univ Technol, Sweden.
    Multimodal Chemical Imaging of Amyloid Plaque Polymorphism Reveals A beta Aggregation Dependent Anionic Lipid Accumulations and Metabolism2018Inngår i: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 90, nr 13, s. 8130-8138Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Amyloid plaque formation constitutes one of the main pathological hallmarks of Alzheimers disease (AD) and is suggested to be a critical factor driving disease pathogenesis. Interestingly, in patients that display amyloid pathology but remain cognitively normal, A beta deposits are predominantly of diffuse morphology suggesting that cored plaque formation is primarily associated with cognitive deterioration and AD pathogenesis. Little is known about the molecular mechanism responsible for conversion of monomeric A beta into neurotoxic aggregates and the predominantly cored deposits observed in AD. The structural diversity among A beta plaques, including cored/compact- and diffuse, may be linked to their distinct A beta profile and other chemical species including neuronal lipids. We developed a novel, chemical imaging paradigm combining matrix assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) and fluorescent amyloid staining. This multimodal imaging approach was used to probe the lipid chemistry associated with structural plaque heterogeneity in transgenic AD mice (tgAPP(Swe)) and was correlated to A beta profiles determined by subsequent laser microdissection and immunoprecipitation-mass spectrometry. Multivariate image analysis revealed an inverse localization of ceramides and their matching metabolites to diffuse and cored structures within single plaques, respectively. Moreover, phosphatidylinositols implicated in AD pathogenesis, were found to localize to the diffuse A beta structures and correlate with A beta 1-42. Further, lysophospholipids implicated in neuroinflammation were increased in all A beta deposits. The results support previous clinical findings on the importance of lipid disturbances in AD pathophysiology and associated sphingolipid processing. These data highlight the potential of multimodal imaging as a powerful technology to probe neuropathological mechanisms.

  • 80.
    Michno, Wojciech
    et al.
    Univ Gothenburg, Sweden.
    Nyström, Sofie
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Wehrli, Patrick
    Univ Gothenburg, Sweden.
    Lashley, Tammaryn
    UCL, England.
    Brinkmalm, Gunnar
    Univ Gothenburg, Sweden.
    Guerard, Laurent
    Univ Gothenburg, Sweden.
    Syvanen, Stina
    Uppsala Univ, Sweden.
    Sehlin, Dag
    Uppsala Univ, Sweden.
    Kaya, Ibrahim
    Univ Gothenburg, Sweden.
    Brinet, Dimitri
    Univ Gothenburg, Sweden.
    Nilsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Hammarström, Per
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Blennow, Kaj
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Zetterberg, Henrik
    Univ Gothenburg, Sweden; UCL, England; Sahlgrens Univ Hosp, Sweden; UCL, England.
    Hanrieder, Jorg
    Univ Gothenburg, Sweden; UCL, England.
    Pyroglutamation of amyloid-x-42 (Ax-42) followed by A1-40 deposition underlies plaque polymorphism in progressing Alzheimers disease pathology2019Inngår i: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 294, nr 17, s. 6719-6732Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Amyloid-β (Aβ) pathology in Alzheimer's disease (AD) is characterized by the formation of polymorphic deposits comprising diffuse and cored plaques. Because diffuse plaques are predominantly observed in cognitively unaffected, amyloid-positive (CU-AP) individuals, pathogenic conversion into cored plaques appears to be critical to AD pathogenesis. Herein, we identified the distinct Aβ species associated with amyloid polymorphism in brain tissue from individuals with sporadic AD (s-AD) and CU-AP. To this end, we interrogated Aβ polymorphism with amyloid conformation–sensitive dyes and a novel in situ MS paradigm for chemical characterization of hyperspectrally delineated plaque morphotypes. We found that maturation of diffuse into cored plaques correlated with increased Aβ1–40 deposition. Using spatial in situ delineation with imaging MS (IMS), we show that Aβ1–40 aggregates at the core structure of mature plaques, whereas Aβ1–42 localizes to diffuse amyloid aggregates. Moreover, we observed that diffuse plaques have increased pyroglutamated Aβx-42 levels in s-AD but not CU-AP, suggesting an AD pathology–related, hydrophobic functionalization of diffuse plaques facilitating Aβ1–40 deposition. Experiments in tgAPPSwe mice verified that, similar to what has been observed in human brain pathology, diffuse deposits display higher levels of Aβ1–42 and that Aβ plaque maturation over time is associated with increases in Aβ1–40. Finally, we found that Aβ1–40 deposition is characteristic for cerebral amyloid angiopathy deposition and maturation in both humans and mice. These results indicate that N-terminal Aβx-42 pyroglutamation and Aβ1–40 deposition are critical events in priming and maturation of pathogenic Aβ from diffuse into cored plaques, underlying neurotoxic plaque development in AD.

  • 81.
    Nilsson, K Peter R
    et al.
    University of Queensland.
    Lovelace, Erica S
    University of Queensland.
    Caesar, Christina E
    University of Queensland.
    Tynngård, Nahreen
    University of Queensland.
    Alewood, Paul F
    University of Queensland.
    Johansson, Helena M
    University of Queensland.
    Sharpe, Iain A
    University of Queensland.
    Lewis, Richard J
    University of Queensland.
    Daly, Norelle L
    University of Queensland.
    Craik, David J
    University of Queensland.
    Solution structure of chi-conopeptide MrIA, a modulator of the human norepinephrine transporter.2005Inngår i: Biopolymers, ISSN 0006-3525, E-ISSN 1097-0282, Vol. 80, nr 6, s. 815-823Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The chi-conopeptides MrIA and MrIB are 13-residue peptides with two disulfide bonds that inhibit human and rat norepinephrine transporter systems and are of significant interest for the design of novel drugs involved in pain treatment. In the current study we have determined the solution structure of MrIA using NMR spectroscopy. The major element of secondary structure is a beta-hairpin with the two strands connected by an inverse gamma-turn. The residues primarily involved in activity have previously been shown to be located in the turn region (Sharpe, I. A.; Palant, E.; Schroder, C. I.; Kaye, D. M.; Adams, D. J.; Alewood, P. F.; Lewis, R. J. J Biol Chem 2003, 278, 40317-40323), which appears to be more flexible than the beta-strands based on disorder in the ensemble of calculated structures. Analogues of MrIA with N-terminal truncations indicate that the N-terminal residues play a role in defining a stable conformation and the native disulfide connectivity. In particular, noncovalent interactions between Val3 and Hyp12 are likely to be involved in maintaining a stable conformation. The N-terminus also affects activity, as a single N-terminal deletion introduced additional pharmacology at rat vas deferens, while deleting the first two amino acids reduced chi-conopeptide potency.

  • 82.
    Nilsson, K.Peter R.
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biomolekylär och Organisk Elektronik. Linköpings universitet, Tekniska högskolan.
    Andersson, M.R.
    Department of Polymer Technology, Chalmers University of Technology, SE-412 96 Göteborg, Sweden.
    Inganäs, Olle
    Linköpings universitet, Tekniska högskolan. Linköpings universitet, Institutionen för fysik, kemi och biologi, Biomolekylär och Organisk Elektronik.
    Conformational transitions in a free amino acid functionalized polythiophene2003Inngår i: Synthetic metals, ISSN 0379-6779, E-ISSN 1879-3290, Vol. 135-136, s. 291-292Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A chiral, 3-substituted polythiophene with an amino acid function shows pH-dependent visible, emission and circular dichroism spectra in buffered aqueous solution. At pH equal to pi of the amino acid, the backbone adopts a non-planar right-handed helical conformation and the polymer chains are separated from each other. Increasing pH leads to a more planar conformation of the backbone and an aggregation of the polymer chains occurs. A lower pH will also lead to a more planar conformation of the backbone, but aggregation of the polymer chains appears to be absent. © 2003 Elsevier Science B.V. All rights reserved.

  • 83.
    Nilsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Tillämpad Fysik. Linköpings universitet, Tekniska högskolan.
    Conjugated polyelectrolytes: conformation sensitive optical probes for the recording of biological processes2005Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The physical properties of conjugated polymers can be utilized for a wide range of biosensors. For instance, the conformational flexibility fouud in conjugated polyelectrolytes, allows direct connection between the geometry of chains and the resulting electronic structure and optical processes, since the extension of the π-conjugated system is distorted by conformational changes of the polyelectrolyte backbone. The biosensors presented in this thesis are utilizing conformational changes of conjugated polyelectrolytes for the detection of biomolecular processes, such as biospecific interactions and conformational changes of biomolecules. The methodology have been used for the detection of DNA-hybridization, single nucleotide polymorphism (SNP) in DNA, conformational alterations of synthetic peptides, conformational alterations of Calmodulin and binding of Ca2+-activated Calmodulin (CaM) to Calcineurin, and amyloid fibril formation of amyloidogenic proteins.

    The method is based on non-covalent assembly of a conjugated polyelectrolyte and a biomolecule of interest. Upon exposure to a second biomolecule recognizing the first biomolecule or a conformational change of the first biomolecule, a conformational alteration of the polyelectrolyte backbone and a change in the electronic properties of the polyelectrolyte occurs, and these alterations can be detected by a change of the absorption or the fluorescence from the polyelectrolyte. Hence, conjugated polyelectrolytes can be used as novel conformation sensitive optical probes for the detection of several biological processes. The biomolecular interaction or the conformational changes of the biomolecule are reflected as an alteration of the geometry and the electronic structure of the bouud polyelectrolyte chains and are detected by absorption and emission. The present mechanism may be used for detection of a variety biomolecular processes, and the simplicity and the diversity of this methodology make it suitable for making inexpensive protein- and DNA-chips for rapid detection of biomolecular recognition.

    Delarbeid
    1. Conformational transitions of a free amino-acid-functionalized polythiophene induced by different buffer systems
    Åpne denne publikasjonen i ny fane eller vindu >>Conformational transitions of a free amino-acid-functionalized polythiophene induced by different buffer systems
    2002 (engelsk)Inngår i: Journal of Physics: Condensed Matter, ISSN 0953-8984, E-ISSN 1361-648X, Vol. 14, nr 42, s. 10011-10020Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    A chiral, 3-substituted polythiophene with an amino-acid function shows pH-dependent visible, emission and circular dichroism spectra in buffered aqueous solution. At pH equal to the pI of the amino-acid, the backbone adopts a nonplanar right-handed helical conformation and the polymer chains are separated from each other. Increasing pH leads to a more planar conformation of the backbone and an aggregation of the polymer chains occurs. A lower pH will also lead to a more planar conformation of the backbone, but aggregation of the polymer chains appears to be absent. The aggregates are disrupted by increasing ionic strength in alkaline buffer systems, indicating hydrogen bonding is important for aggregation. On the other hand, ions containing an amino group and one or more hydroxyl groups induce a more planar conformation of the polymer backbone.

    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-46886 (URN)10.1088/0953-8984/14/42/313 (DOI)
    Tilgjengelig fra: 2009-10-11 Laget: 2009-10-11 Sist oppdatert: 2017-12-13
    2. Chip and solution detection of DNA hybridization using a luminescent zwitterionic polythiophene derivative
    Åpne denne publikasjonen i ny fane eller vindu >>Chip and solution detection of DNA hybridization using a luminescent zwitterionic polythiophene derivative
    2003 (engelsk)Inngår i: Nature Materials, ISSN 1476-1122, E-ISSN 1476-4660, Vol. 2, nr 6, s. 419-424Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Electronic polymers in aqueous media may offer bioelectronic detection of biospecific interactions. Here we report a fluorometric DNA hybridization detection method based on non-covalent coupling of DNA to a water-soluble zwitterionic polythiophene derivative. Introduction of a single-stranded oligonucleotide will induce a planar polymer and aggregation of the polymer chains, detected as a decrease of the intensity and a red-shift of the fluorescence. On addition of a complementary oligonucleotide, the intensity of the emitted light is increased and blue-shifted. The detection limit of this method is at present ~10−11 moles. The method is highly sequence specific, and a single-nucleotide mismatch can be detected within five minutes without using any denaturation steps. The interaction with DNA and the optical phenomena persists when the polymer is deposited and patterned on a surface. This offers a novel way to create DNA chips without using covalent attachment of the receptor or labelling of the analyte.

    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-46558 (URN)10.1038/nmat899 (DOI)
    Tilgjengelig fra: 2009-10-11 Laget: 2009-10-11 Sist oppdatert: 2017-12-13
    3. Self-assembly of synthetic peptides control conformation and optical properties of a zwitterionic polythiophene derivative
    Åpne denne publikasjonen i ny fane eller vindu >>Self-assembly of synthetic peptides control conformation and optical properties of a zwitterionic polythiophene derivative
    2003 (engelsk)Inngår i: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 100, nr 18, s. 10170-10174Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    The optical transitions of a chiral, three-substituted polythiophene with an amino acid function can be tuned by interactions with synthetic peptides. The addition of a positively charged peptide with a random-coil formation will force the polymer to adopt a nonplanar conformation, and the intensity of the emitted light is increased and blue-shifted. After the addition of a negatively charged peptide with a random-coil conformation, the backbone of the polymer adopts a planar conformation and an aggregation of the polymer chains occurs, seen as a red shift and a decrease of the intensity of the emitted light. By adding the positively charged peptide designed to form a four-helix bundle with the negatively charged peptide, the polymer aggregates are disrupted and the intensity of the emitted light is increased because of separation of the polymer chains. This technique could be used as a platform for making novel sensors and biomolecular switches.

    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-14039 (URN)10.1073/pnas.1834422100 (DOI)
    Tilgjengelig fra: 2006-09-28 Laget: 2006-09-28 Sist oppdatert: 2017-12-13
    4. Twisting macromolecular chains: self-assembly of a chiral supermolecule from nonchiral polythiophene polyanions and random-coil synthetic peptides
    Åpne denne publikasjonen i ny fane eller vindu >>Twisting macromolecular chains: self-assembly of a chiral supermolecule from nonchiral polythiophene polyanions and random-coil synthetic peptides
    2004 (engelsk)Inngår i: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 101, nr 31, s. 11197-11202Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    The self-assembly of a negatively charged conjugated polythiophene derivative and a positively charged synthetic peptide will create a chiral, well ordered supermolecule. This supermolecule has the three-dimensional ordered structure of a biomolecule and the electronic properties of a conjugated polymer. The molecular complex being formed clearly affects the conformation of the polymer backbone. A main-chain chirality, such as a predominantly one-handed helical structure induced by the acid–base complexation between the conjugated polymer and the synthetic peptide, is seen. The alteration of the polymer backbone influences the optical properties of the polymer, seen as changes in the absorption, emission, and Raman spectra of the polymer. The complexation of the polythiophene and the synthetic peptide also induce a change from random-coil to helical structure of the synthetic peptide. The supermolecule described in this article may be used in a wide range of applications such as biomolecular devices, artificial enzymes, and biosensors.

    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-45666 (URN)10.1073/pnas.0401853101 (DOI)
    Tilgjengelig fra: 2009-10-11 Laget: 2009-10-11 Sist oppdatert: 2017-12-13
    5. Enantiomeric substituents determine the chirality of luminescent conjugated polythiophenes
    Åpne denne publikasjonen i ny fane eller vindu >>Enantiomeric substituents determine the chirality of luminescent conjugated polythiophenes
    2004 (engelsk)Inngår i: Macromolecules, ISSN 0024-9297, E-ISSN 1520-5835, Vol. 37, nr 17, s. 6316-6321Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Chiral isomers of 3-substituted polythiophenes with amino acid functiontionalized side chains are compared. The polymers show pH-dependent absorption, emission, and circular dichroism spectra in buffered aqueous solution. At pH equal to pI of the amino acid, the backbones adopt nonplanar helical conformations, and the polymer chains are separated from each other. Increasing pH leads to more planar conformations of the backbones and an aggregation of the polymer chains occurs. A lower pH will also lead to more planar conformation of the backbones, but aggregation of the polymer chains appears to be absent. The nonplanar to planar transition of the polymer backbone and the separation/aggregation of different polymer chains is not affected by stereochemistry of the zwitterionic side chain. The two isomers have almost identical pH-dependent absorption and emission spectra. However, the chirality of the zwitterionic side chain is reflected in the conformation of the polymer backbone, giving rise to a right-handed and left-handed helical form of polythiophene chains since the induced circular dichroism patterns of the two polymers are mirror images.

    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-45660 (URN)10.1021/ma048859e (DOI)
    Tilgjengelig fra: 2009-10-11 Laget: 2009-10-11 Sist oppdatert: 2017-12-13
    6. Optical emission of a conjugated polyelectrolyte: calcium-induced conformational changes in calmodulin and calmodulin-calcineurin interactions
    Åpne denne publikasjonen i ny fane eller vindu >>Optical emission of a conjugated polyelectrolyte: calcium-induced conformational changes in calmodulin and calmodulin-calcineurin interactions
    2004 (engelsk)Inngår i: Macromolecules, ISSN 0024-9297, E-ISSN 1520-5835, Vol. 37, nr 24, s. 9109-9113Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Electronic polymers in aqueous media offer bioelectronic detection of biomolecular processes. Here we report fluorometric detection of calcium-induced conformational changes in calmodulin based on noncovalent assembly of calmodulin to a water-soluble zwitterionic polythiophene derivative. Assembly with calmodulin will induce a planar geometry and aggregation of the polymer chains, detected as a decrease of the intensity and a red shift of the fluorescence. Upon addition of Ca2+ the intensity of the emitted light is increased and blue-shifted. The geometrical alteration of the polymer chains can further be utilized for recording of the binding of calcineurin to the calcium-activated POWT−calmodulin complex. This novel methodology, using a conformation-sensitive probe, allows fluorometric detection of conformational changes in biomolecules and protein−protein interactions without any covalent modifications of the biomolecules. The rapid and selective method is based on noncovalent interactions between a zwitterionic polythiophene derivative and the biomolecule of interest. This offers a novel way to create microarrays without using covalent attachment of the receptor or labeling of the analyte.

    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-45577 (URN)10.1021/ma048605t (DOI)
    Tilgjengelig fra: 2009-10-11 Laget: 2009-10-11 Sist oppdatert: 2017-12-13
    7. Conjugated polyelectrolytes: conformation-sensitive optical probes for detection of amyloid fibril formation
    Åpne denne publikasjonen i ny fane eller vindu >>Conjugated polyelectrolytes: conformation-sensitive optical probes for detection of amyloid fibril formation
    2005 (engelsk)Inngår i: Biochemistry, ISSN 0006-2960, E-ISSN 1520-4995, Vol. 44, nr 10, s. 3718-3724Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    The in vivo deposition of amyloid fibrils is a hallmark of many devastating diseases known as the amyloidoses. Amyloid formation in vitro may also complicate production of proteins in the biotechnology industry. Simple, sensitive, and versatile tools that detect the fibrillar conformation of amyloidogenic proteins are thus of great importance. We have developed a negatively charged conjugated polyelectrolyte that displays different characteristic optical changes, detected visually or by absorption and emission, depending on whether the protein with which it forms a complex is in its native state or amyloid fibril conformation. This simple, rapid, and novel methodology was applied here to two amyloidogenic proteins, insulin and lysozyme, and its validity for detection of their fibrillar conformation was verified by currently used methods such as circular dichroism, transmission electron microscopy, and Congo red absorption.

    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-14599 (URN)10.1021/bi047402u (DOI)
    Tilgjengelig fra: 2007-10-12 Laget: 2007-10-12 Sist oppdatert: 2018-04-25
  • 84.
    Nilsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    Luminescent Conjugated Polymers for Staining and Characterization of Amyloid Deposits2009Inngår i: Organic electronics in sensors and biotechnology / [ed] Ruth Shinar, Joseph Shinar, McGraw-Hill, 2009, 1, s. 448-Kapittel i bok, del av antologi (Fagfellevurdert)
    Abstract [en]

    The latest in organic electronics-based sensing and biotechnologyDevelop high-performance, field-deployable organic semiconductor-based biological, chemical, and physical sensor arrays using the comprehensive information contained in this definitive volume. Organic Electronics in Sensors and Biotechnology presents state-of-the-art technology alongside real-world applications and ongoing R & D. Learn about light, temperature, and pressure monitors, integrated flexible pyroelectric sensors, sensing of organic and inorganic compounds, and design of compact photoluminescent sensors. You will also get full details on organic lasers, organic electronics in memory elements, disease and pathogen detection, and conjugated polymers for advancing cellular biology.Monitor organic and inorganic compounds with OFETs Characterize organic materials using impedance spectroscopyWork with organic LEDs, photodetectors, and photovoltaic cellsForm flexible pyroelectric sensors integrated with OFETs Build PL-based chemical and biological sensing modules and arraysDesign organic semiconductor lasers and memory elements Use luminescent conjugated polymers as optical biosensors Deploy polymer-based switches and ion pumps at the microfluidic level

  • 85.
    Nilsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    Small organic probes as amyloid specific ligands - Past and recent molecular scaffolds2009Inngår i: FEBS Letters, ISSN 0014-5793, Vol. 583, nr 16, s. 2593-2599Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Molecular probes for selective staining and imaging of protein aggregates, such as amyloid, are important to advance our understanding of the molecular mechanisms underlying protein misfolding diseases and also for obtaining an early and accurate clinical diagnosis of these disorders. Since normal immunohistochemical reagents, such as antibodies have shown limitation for identifying protein aggregates both in vitro and in vivo, small organic probes have been utilized as amyloid specific markers. In this review, past and recent molecular scaffolds that have been utilized for the development of small organic amyloid imaging agents are discussed.

  • 86.
    Nilsson, Peter
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biomolekylär och Organisk Elektronik. Linköpings universitet, Tekniska högskolan.
    Andersson, M.R.
    Department of Polymer Technology, Chalmers University of Technology, Göteborg, Sweden.
    Inganäs, Olle
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biomolekylär och Organisk Elektronik. Linköpings universitet, Tekniska högskolan.
    Conformational transitions of a free amino-acid-functionalized polythiophene induced by different buffer systems2002Inngår i: Journal of Physics: Condensed Matter, ISSN 0953-8984, E-ISSN 1361-648X, Vol. 14, nr 42, s. 10011-10020Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A chiral, 3-substituted polythiophene with an amino-acid function shows pH-dependent visible, emission and circular dichroism spectra in buffered aqueous solution. At pH equal to the pI of the amino-acid, the backbone adopts a nonplanar right-handed helical conformation and the polymer chains are separated from each other. Increasing pH leads to a more planar conformation of the backbone and an aggregation of the polymer chains occurs. A lower pH will also lead to a more planar conformation of the backbone, but aggregation of the polymer chains appears to be absent. The aggregates are disrupted by increasing ionic strength in alkaline buffer systems, indicating hydrogen bonding is important for aggregation. On the other hand, ions containing an amino group and one or more hydroxyl groups induce a more planar conformation of the polymer backbone.

  • 87.
    Nilsson, Peter
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    Hammarström, Per
    Linköpings universitet, Tekniska högskolan. Linköpings universitet, Institutionen för fysik, kemi och biologi, Biokemi.
    Luminescent conjugated polymers: Illuminating the dark matters of biology and pathology2008Inngår i: Advanced Materials, ISSN 0935-9648, E-ISSN 1521-4095, Vol. 20, nr 13, s. 2639-2645Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Novel technologies for studying biological events are of great interest and luminescent conjugated polymers (LCPs), a material normally used in organic electronics, have proven useful for the detection of a wide range of disease-related biological processes. The conformation-sensitive optical properties of LCPs provide the ability to study the biochemical activity of biological events on the basis of a structure-function relation, rather than a molecular basis. In this Research News article, the LCP technique and its usefulness for studying protein aggregation diseases are highlighted. We also discuss the much-needed illuminating insights of the underlying pathological events regarding protein aggregation diseases. In addition, essential future basic research advances that relate to further development of LCPs as molecular probes are presented. We also confer the intriguing prospect of employing amyloid fibrils, that is, a symmetric stable nanomaterial normally associated with the dark side of horrific pathology, as a scaffold for functional polymer-protein hybrid materials. © 2008 WILEY-VCH Verlag GmbH & Co. KGaA.

  • 88.
    Nilsson, Peter
    et al.
    Linköpings universitet, Tekniska högskolan. Linköpings universitet, Institutionen för fysik, kemi och biologi, Biomolekylär och Organisk Elektronik.
    Hammarström, Per
    Linköpings universitet, Tekniska högskolan. Linköpings universitet, Institutionen för fysik, kemi och biologi, Biokemi.
    Ahlgren, Fredrik
    Division of Cell Biology Linköpings universitet.
    Herland, Anna
    Linköpings universitet, Tekniska högskolan. Linköpings universitet, Institutionen för fysik, kemi och biologi, Biomolekylär och Organisk Elektronik.
    Schnell, Edrun A
    The Norwegian University of Science and Technology.
    Lindgren, Mikael
    The Norwegian University of Science and Technology.
    Westermark, Gunilla
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för medicinsk cellbiologi.
    Inganäs, Olle
    Linköpings universitet, Tekniska högskolan. Linköpings universitet, Institutionen för fysik, kemi och biologi, Biomolekylär och Organisk Elektronik.
    Conjugated Polyelectrolytes - Conformation - Sensitive Optical Probes for staining and Characterization of Amyloid Deposits2006Inngår i: ChemBioChem (Print), ISSN 1439-4227, E-ISSN 1439-7633, Vol. 7, s. 1096-1104Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

      

  • 89.
    Nilsson, Peter
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biomolekylär och Organisk Elektronik. Linköpings universitet, Tekniska högskolan.
    Herland, Anna
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biomolekylär och Organisk Elektronik. Linköpings universitet, Tekniska högskolan.
    Hammarström, Per
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biokemi. Linköpings universitet, Tekniska högskolan.
    Inganäs, Olle
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biomolekylär och Organisk Elektronik. Linköpings universitet, Tekniska högskolan.
    Conjugated polyelectrolytes: conformation-sensitive optical probes for detection of amyloid fibril formation2005Inngår i: Biochemistry, ISSN 0006-2960, E-ISSN 1520-4995, Vol. 44, nr 10, s. 3718-3724Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The in vivo deposition of amyloid fibrils is a hallmark of many devastating diseases known as the amyloidoses. Amyloid formation in vitro may also complicate production of proteins in the biotechnology industry. Simple, sensitive, and versatile tools that detect the fibrillar conformation of amyloidogenic proteins are thus of great importance. We have developed a negatively charged conjugated polyelectrolyte that displays different characteristic optical changes, detected visually or by absorption and emission, depending on whether the protein with which it forms a complex is in its native state or amyloid fibril conformation. This simple, rapid, and novel methodology was applied here to two amyloidogenic proteins, insulin and lysozyme, and its validity for detection of their fibrillar conformation was verified by currently used methods such as circular dichroism, transmission electron microscopy, and Congo red absorption.

  • 90.
    Nilsson, Peter
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    Ikenberg, Kristian
    University Hospital of Zurich.
    Åslund, Andreas
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    Fransson, Sophia
    Konradsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    Röcken, Christoph
    Christian-Albrechts-University, Kiel.
    Moch, Holger
    University Hospital of Zurich.
    Aguzzi, Adriano
    University Hospital of Zurich.
    Structural typing of systemic amyloidoses by luminescent-conjugated polymer spectroscopy.2010Inngår i: The American journal of pathology, ISSN 1525-2191, Vol. 176, nr 2, s. 563-574Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Most systemic amyloidoses are progressive and lethal, and their therapy depends on the identification of the offending proteins. Here we report that luminescent-conjugated thiophene polymers (LCP) sensitively detect amyloid deposits. The heterodisperse polythiophene acetic acid derivatives, polythiophene acetic acid (PTAA) and trimeric PTAA, emitted yellow-red fluorescence on binding to amyloid deposits, whereas chemically homogeneous pentameric formic thiophene acetic acid emitted green-yellow fluorescence. The geometry of LCPs modulates the spectral composition of the emitted light, thereby reporting ligand-induced steric changes. Accordingly, a screen of PTAA-stained amyloid deposits in histological tissue arrays revealed striking spectral differences between specimens. Blinded cluster assignments of spectral profiles of tissue samples from 108 tissue samples derived from 96 patients identified three nonoverlapping classes, which were found to match AA, AL, and ATTR immunotyping. We conclude that LCP spectroscopy is a sensitive and powerful tool for identifying and characterizing amyloid deposits.

  • 91.
    Nilsson, Peter
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biomolekylär och Organisk Elektronik. Linköpings universitet, Tekniska högskolan.
    Inganäs, Olle
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biomolekylär och Organisk Elektronik. Linköpings universitet, Tekniska högskolan.
    Chip and solution detection of DNA hybridization using a luminescent zwitterionic polythiophene derivative2003Inngår i: Nature Materials, ISSN 1476-1122, E-ISSN 1476-4660, Vol. 2, nr 6, s. 419-424Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Electronic polymers in aqueous media may offer bioelectronic detection of biospecific interactions. Here we report a fluorometric DNA hybridization detection method based on non-covalent coupling of DNA to a water-soluble zwitterionic polythiophene derivative. Introduction of a single-stranded oligonucleotide will induce a planar polymer and aggregation of the polymer chains, detected as a decrease of the intensity and a red-shift of the fluorescence. On addition of a complementary oligonucleotide, the intensity of the emitted light is increased and blue-shifted. The detection limit of this method is at present ~10−11 moles. The method is highly sequence specific, and a single-nucleotide mismatch can be detected within five minutes without using any denaturation steps. The interaction with DNA and the optical phenomena persists when the polymer is deposited and patterned on a surface. This offers a novel way to create DNA chips without using covalent attachment of the receptor or labelling of the analyte.

  • 92.
    Nilsson, Peter
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi. Linköpings universitet, Tekniska högskolan.
    Inganäs, Olle
    Linköpings universitet, Institutionen för fysik, kemi och biologi. Linköpings universitet, Tekniska högskolan.
    Optical emission of a conjugated polyelectrolyte: calcium-induced conformational changes in calmodulin and calmodulin-calcineurin interactions2004Inngår i: Macromolecules, ISSN 0024-9297, E-ISSN 1520-5835, Vol. 37, nr 24, s. 9109-9113Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Electronic polymers in aqueous media offer bioelectronic detection of biomolecular processes. Here we report fluorometric detection of calcium-induced conformational changes in calmodulin based on noncovalent assembly of calmodulin to a water-soluble zwitterionic polythiophene derivative. Assembly with calmodulin will induce a planar geometry and aggregation of the polymer chains, detected as a decrease of the intensity and a red shift of the fluorescence. Upon addition of Ca2+ the intensity of the emitted light is increased and blue-shifted. The geometrical alteration of the polymer chains can further be utilized for recording of the binding of calcineurin to the calcium-activated POWT−calmodulin complex. This novel methodology, using a conformation-sensitive probe, allows fluorometric detection of conformational changes in biomolecules and protein−protein interactions without any covalent modifications of the biomolecules. The rapid and selective method is based on noncovalent interactions between a zwitterionic polythiophene derivative and the biomolecule of interest. This offers a novel way to create microarrays without using covalent attachment of the receptor or labeling of the analyte.

  • 93.
    Nilsson, Peter
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biomolekylär och Organisk Elektronik. Linköpings universitet, Tekniska högskolan.
    Inganäs, Olle
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biomolekylär och Organisk Elektronik. Linköpings universitet, Tekniska högskolan.
    Optical sensors based on conjugated polymers2007Inngår i: Handbook of conducting polymers (Third Edition) / [ed] Terje A. Skotheim,John Reynolds, CRC Press, 2007, 3, s. -1680Kapittel i bok, del av antologi (Fagfellevurdert)
    Abstract [en]

    Learn how recent advances are fueling new possibilities in textiles, optics, electronics, and biomedicine!

    As the field of conjugated, electrically conducting, and electroactive polymers has grown, the Handbook of Conducting Polymershas been there to document and celebrate these changes along the way. Now split into two volumes, this new edition continues to provide the expertise of world-renowned contributors while maintaining the clear format of previous editions as it incorporates the latest developments in both the fundamental science and practical applications of polymers.

    The first volume in the set focuses on the concepts and basic physical aspects needed to understand the behavior and performance of conjugated polymers. The book describes the theories behind π-conjugated materials and electron–lattice dynamics in organic systems. It also details synthesis methods and electrical and physical properties of the entire family of conducting polymers.

    Picking up where the first volume left off, the second volume concentrates on the numerous processing methods for conducting polymers and their integration into various devices and applications. It first examines coating, printing, and spinning methods for complex patterned films and fibers. The book then shows how conducting and semiconducting polymers are applied in many devices, such as light-emitting displays, solar cells, field effect transistors, electrochromic panels, charge storage devices, biosensors, and actuators.

    As the science of conjugated and conducting polymers progresses, further applications will be realized, fueling greater possibilities in textiles, optics, electronics, and biomedicine. This handbook will be there to provide essential information on polymers as well as the most up-to-date developments.

  • 94.
    Nilsson, Peter
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Joshi-Barr, Shivanjali
    University of California San Diego.
    Winson, Olivia
    University of California San Diego.
    Sigurdson, Christina J
    University of California San Diego.
    Prion Strain Interactions Are Highly Selective2010Inngår i: JOURNAL OF NEUROSCIENCE, ISSN 0270-6474, Vol. 30, nr 36, s. 12094-12102Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Various misfolded and aggregated neuronal proteins commonly coexist in neurodegenerative disease, but whether the proteins coaggregate and alter the disease pathogenesis is unclear. Here we used mixtures of distinct prion strains, which are believed to differ in conformation, to test the hypothesis that two different aggregates interact and change the disease in vivo. We tracked two prion strains in mice histopathologically and biochemically, as well as by spectral analysis of plaque-bound PTAA (polythiophene acetic acid), a conformation-sensitive fluorescent amyloid ligand. We found that prion strains interacted in a highly selective and strain-specific manner, with (1) no interaction, (2) hybrid plaque formation, or (3) blockage of one strain by a second (interference). The hybrid plaques were maintained on additional passage in vivo and each strain seemed to maintain its original conformational properties, suggesting that one strain served only as a scaffold for aggregation of the second strain. These findings not only further our understanding of prion strain interactions but also directly demonstrate interactions that may occur in other protein aggregate mixtures.

  • 95.
    Nilsson, Peter
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Lindgren, Mikael
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Hammarstrom, Per
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    A pentameric luminescent-conjugated oligothiophene for optical imaging of in vitro-formed amyloid fibrils and protein aggregates in tissue sections.2012Inngår i: Methods in molecular biology (Clifton, N.J.), ISSN 1940-6029, Vol. 849, s. 425-434Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Luminescent-conjugated oligo- and polythiophenes (LCOs and LCPs) are valuable tools for optical imaging of a plethora of protein aggregates associated with amyloidoses. Here, we describe the utilization of an anionic pentameric LCO, p-FTAA, for staining of protein aggregates in a variety of platforms, including in vitro-formed amyloid fibrils and tissue sections.

  • 96.
    Nilsson, Peter
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Lindgren, Mikael
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten. Department of Physics, The Norwegian University of Science and Technology, 7491, Trondheim, Norway.
    Hammarström, Per
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Luminescent-Conjugated Oligothiophene Probe Applications for Fluorescence Imaging of Pure Amyloid Fibrils and Protein Aggregates in Tissues2018Inngår i: Amyloid Proteins: Methods and Protocols / [ed] Einar M. Sigurdsson, Miguel Calero and María Gasset, Humana Press, 2018, Vol. 1779, s. 485-496Kapittel i bok, del av antologi (Fagfellevurdert)
    Abstract [en]

    Luminescent-conjugated oligo- and polythiophenes (LCOs and LCPs) are valuable tools for optical imaging of a plethora of protein aggregates associated with amyloidoses. Here, we outline updated protocols for the application of the anionic pentameric LCO, p-FTAA, for staining and hyperspectral imaging of protein aggregates in a variety of settings such as in vitro formed amyloid fibrils, ex vivo tissue sections, and whole brain Drosophila.

  • 97.
    Nilsson, Peter
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi. Linköpings universitet, Tekniska högskolan.
    Olsson, Johan
    Linköpings universitet, Institutionen för fysik, kemi och biologi. Linköpings universitet, Tekniska högskolan.
    Konradsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi. Linköpings universitet, Tekniska högskolan.
    Inganäs, Olle
    Linköpings universitet, Institutionen för fysik, kemi och biologi. Linköpings universitet, Tekniska högskolan.
    Enantiomeric substituents determine the chirality of luminescent conjugated polythiophenes2004Inngår i: Macromolecules, ISSN 0024-9297, E-ISSN 1520-5835, Vol. 37, nr 17, s. 6316-6321Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Chiral isomers of 3-substituted polythiophenes with amino acid functiontionalized side chains are compared. The polymers show pH-dependent absorption, emission, and circular dichroism spectra in buffered aqueous solution. At pH equal to pI of the amino acid, the backbones adopt nonplanar helical conformations, and the polymer chains are separated from each other. Increasing pH leads to more planar conformations of the backbones and an aggregation of the polymer chains occurs. A lower pH will also lead to more planar conformation of the backbones, but aggregation of the polymer chains appears to be absent. The nonplanar to planar transition of the polymer backbone and the separation/aggregation of different polymer chains is not affected by stereochemistry of the zwitterionic side chain. The two isomers have almost identical pH-dependent absorption and emission spectra. However, the chirality of the zwitterionic side chain is reflected in the conformation of the polymer backbone, giving rise to a right-handed and left-handed helical form of polythiophene chains since the induced circular dichroism patterns of the two polymers are mirror images.

  • 98.
    Nilsson, Peter
    et al.
    Linköpings universitet, Tekniska högskolan. Linköpings universitet, Institutionen för fysik, kemi och biologi, Biomolekylär och Organisk Elektronik.
    Olsson, Johan
    Linköpings universitet, Institutionen för fysik, kemi och biologi. Linköpings universitet, Tekniska högskolan.
    Stabo-Eeg, Franz
    The Norwegian University of Scinece and Technology.
    Lindgren, Mikael
    The Norwegian University of Science and Technology.
    Konradsson, Peter
    Linköpings universitet, Tekniska högskolan. Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi.
    Inganäs, Olle
    Linköpings universitet, Tekniska högskolan. Linköpings universitet, Institutionen för fysik, kemi och biologi, Biomolekylär och Organisk Elektronik.
    Chiral Recognition of a Synthetic Peptide Using Enantiomeric Conjugated Polyelectrolytes and Optical Spectroscopy2005Inngår i: Macromolecules, ISSN 0024-9297, E-ISSN 1520-5835, Vol. 38, s. 6813-6821Artikkel i tidsskrift (Fagfellevurdert)
  • 99.
    Nilsson, Peter
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biomolekylär och Organisk Elektronik. Linköpings universitet, Tekniska högskolan.
    Rydberg, Johan
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    Baltzer, Lars
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    Inganäs, Olle
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biomolekylär och Organisk Elektronik. Linköpings universitet, Tekniska högskolan.
    Self-assembly of synthetic peptides control conformation and optical properties of a zwitterionic polythiophene derivative2003Inngår i: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 100, nr 18, s. 10170-10174Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The optical transitions of a chiral, three-substituted polythiophene with an amino acid function can be tuned by interactions with synthetic peptides. The addition of a positively charged peptide with a random-coil formation will force the polymer to adopt a nonplanar conformation, and the intensity of the emitted light is increased and blue-shifted. After the addition of a negatively charged peptide with a random-coil conformation, the backbone of the polymer adopts a planar conformation and an aggregation of the polymer chains occurs, seen as a red shift and a decrease of the intensity of the emitted light. By adding the positively charged peptide designed to form a four-helix bundle with the negatively charged peptide, the polymer aggregates are disrupted and the intensity of the emitted light is increased because of separation of the polymer chains. This technique could be used as a platform for making novel sensors and biomolecular switches.

  • 100.
    Nilsson, Peter
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biomolekylär och Organisk Elektronik. Linköpings universitet, Tekniska högskolan.
    Rydberg, Johan
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    Baltzer, Lars
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biomolekylär och Organisk Elektronik. Linköpings universitet, Tekniska högskolan.
    Inganäs, Olle
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biomolekylär och Organisk Elektronik. Linköpings universitet, Tekniska högskolan.
    Twisting macromolecular chains: self-assembly of a chiral supermolecule from nonchiral polythiophene polyanions and random-coil synthetic peptides2004Inngår i: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 101, nr 31, s. 11197-11202Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The self-assembly of a negatively charged conjugated polythiophene derivative and a positively charged synthetic peptide will create a chiral, well ordered supermolecule. This supermolecule has the three-dimensional ordered structure of a biomolecule and the electronic properties of a conjugated polymer. The molecular complex being formed clearly affects the conformation of the polymer backbone. A main-chain chirality, such as a predominantly one-handed helical structure induced by the acid–base complexation between the conjugated polymer and the synthetic peptide, is seen. The alteration of the polymer backbone influences the optical properties of the polymer, seen as changes in the absorption, emission, and Raman spectra of the polymer. The complexation of the polythiophene and the synthetic peptide also induce a change from random-coil to helical structure of the synthetic peptide. The supermolecule described in this article may be used in a wide range of applications such as biomolecular devices, artificial enzymes, and biosensors.

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