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Lindgren, Mikael
Alternative names
Publications (10 of 18) Show all publications
Zhang, J., Wang, J., Sandberg, A., Wu, X., Nyström, S., LeVine, H. I., . . . Lindgren, M. (2018). Intramolecular Proton and Charge Transfer of Pyrene-based trans-Stilbene Salicylic Acids Applied to Detection of Aggregated Proteins.. ChemPhysChem, 19(22), 3001-3009
Open this publication in new window or tab >>Intramolecular Proton and Charge Transfer of Pyrene-based trans-Stilbene Salicylic Acids Applied to Detection of Aggregated Proteins.
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2018 (English)In: ChemPhysChem, ISSN 1439-4235, E-ISSN 1439-7641, Vol. 19, no 22, p. 3001-3009Article in journal (Refereed) Published
Abstract [en]

Two analogues to the fluorescent amyloid probe 2,5-bis(4'-hydroxy-3'-carboxy-styryl)benzene (X-34) were synthesized based on the trans-stilbene pyrene scaffold (Py1SA and Py2SA). The compounds show strikingly different emission spectra when bound to preformed Aβ1-42 fibrils. This remarkable emission difference is retained when bound to amyloid fibrils of four distinct proteins, suggesting a common binding configuration for each molecule. Density functional theory calculations show that Py1SA is twisted, while Py2SA is more planar. Still, an analysis of the highest occupied molecular orbitals (HOMOs) and lowest unoccupied molecular orbitals (LUMOs) of the two compounds indicates that the degree of electronic coupling between the pyrene and salicylic acid (SA) moieties is larger in Py1SA than in Py2SA. Excited state intramolecular proton transfer (ESIPT) coupled-charge transfer (ICT) was observed for the anionic form in polar solvents. We conclude that ICT properties of trans-stilbene derivatives can be utilized for amyloid probe design with large changes in emission spectra and decay times from analogous chemical structures depending on the detailed physical nature of the binding site.less thanbr /greater than (© 2018 Wiley-VCH Verlag GmbH and Co. KGaA, Weinheim.)

Place, publisher, year, edition, pages
Weinheim, Germany: Wiley-VCH Verlag, 2018
National Category
Theoretical Chemistry
Identifiers
urn:nbn:se:liu:diva-152767 (URN)10.1002/cphc.201800823 (DOI)000450672100006 ()30183138 (PubMedID)
Available from: 2018-11-20 Created: 2018-11-20 Last updated: 2018-12-10
Nilsson, P., Lindgren, M. & Hammarström, P. (2018). Luminescent-Conjugated Oligothiophene Probe Applications for Fluorescence Imaging of Pure Amyloid Fibrils and Protein Aggregates in Tissues. In: Einar M. Sigurdsson, Miguel Calero and María Gasset (Ed.), Amyloid Proteins: Methods and Protocols (pp. 485-496). Humana Press, 1779
Open this publication in new window or tab >>Luminescent-Conjugated Oligothiophene Probe Applications for Fluorescence Imaging of Pure Amyloid Fibrils and Protein Aggregates in Tissues
2018 (English)In: Amyloid Proteins: Methods and Protocols / [ed] Einar M. Sigurdsson, Miguel Calero and María Gasset, Humana Press, 2018, Vol. 1779, p. 485-496Chapter in book (Refereed)
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.

Place, publisher, year, edition, pages
Humana Press, 2018
Series
Methods in Molecular Biology, ISSN 1064-3745, E-ISSN 1940-6029 ; 1779
Keywords
Amyloid; Fluorescence imaging; Luminescent-conjugated oligothiophenes; Protein aggregates; p-FTAA
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:liu:diva-152516 (URN)10.1007/978-1-4939-7816-8_30 (DOI)29886552 (PubMedID)9781493978151 (ISBN)9781493978168 (ISBN)
Available from: 2019-03-28 Created: 2019-03-28 Last updated: 2019-03-29
Bogoeva, V., Siksjö, M., Säterbo, K. G., Melo, T. B., Björköy, A., Lindgren, M. & Gederaas, O. A. (2016). Ruthenium porphyrin-induced photodamage in bladder cancer cells. Photodiagnosis and Photodynamic Therapy, 14
Open this publication in new window or tab >>Ruthenium porphyrin-induced photodamage in bladder cancer cells
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2016 (English)In: Photodiagnosis and Photodynamic Therapy, ISSN 1572-1000, E-ISSN 1873-1597, Vol. 14Article in journal (Refereed) Published
Abstract [en]

Photodynamic therapy (PDT) is a noninvasive treatment for solid malignant and flat tumors. Light activated sensitizers catalyze photochemical reactions that produce reactive oxygen species which can cause cancer cell death. In this work we investigated the photophysical properties of the photosensitizer ruthenium(II) porphyrin (RuP), along with its PDT efficiency onto rat bladder cancer cells (AY27). Optical spectroscopy verified that RuP is capable to activate singlet oxygen via blue and red absorption bands and inter system crossing (ISC) to the triplet state. In vitro experiments on AY27 indicated increased photo-toxicity of RuP (20 mu M, 1811 incubation) after cell illumination (at 435 nm), as a function of blue light exposure. Cell survival fraction was significantly reduced to 14% after illumination of 20 mu M RuP with 15.6 J/cm(2), whereas the "dark toxicity" of 20 mu M RuP was 17%. Structural and morphological changes of cells were observed, due to RuP accumulation, as well as light-dependent cell death was recorded by confocal microscopy. Flow cytometry verified that PDT-RuP (50 mu M) triggered significant photo-induced cellular destruction with a photoxicity of (93% +/- 0.9%). Interestingly, the present investigation of RuP-PDT showed that the dominating mode of cell death is necrosis. RuP "dark toxicity" compared to the conventional chemotherapeutic drug cisplatin was higher, both evaluated by the MIT assay (24 h). In conclusion, the present investigation shows that RuP with or without photoactivation induces cell death of bladder cancer cells. (C) 2016 Elsevier B.V. All rights reserved.

Place, publisher, year, edition, pages
ELSEVIER SCIENCE BV, 2016
Keywords
Photodynamic therapy; PDT; Ruthenium porphyrin; Photophysical characterization; Singlet oxygen; Bladder cancer
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:liu:diva-130436 (URN)10.1016/j.pdpdt.2016.01.012 (DOI)000379372900003 ()26845686 (PubMedID)
Note

Funding Agencies|Cancer Research Foundation of St. Olavs University Hospital, Trondheim, Norway; Linkoping University Cancer Foundation; EEA grant

Available from: 2016-08-07 Created: 2016-08-05 Last updated: 2017-11-28
Shirani, H., Linares, M., Sigurdson, C. J., Lindgren, M., Norman, P. & Nilsson, P. (2015). A Palette of Fluorescent Thiophene-Based Ligands for the Identification of Protein Aggregates. Chemistry - A European Journal, 21(43), 15133-15137
Open this publication in new window or tab >>A Palette of Fluorescent Thiophene-Based Ligands for the Identification of Protein Aggregates
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2015 (English)In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 21, no 43, p. 15133-15137Article in journal (Refereed) Published
Abstract [en]

By replacing the central thiophene unit of an anionic pentameric oligothiophene with other heterocyclic moities, a palette of pentameric thiophene-based ligands with distinct fluorescent properties were synthesized. All ligands displayed superior selectivity towards recombinant amyloid fibrils as well as disease-associated protein aggregates in tissue sections.

Place, publisher, year, edition, pages
WILEY-V C H VERLAG GMBH, 2015
Keywords
Alzheimers disease; fluorescent probes; luminescence; oligothiophenes; microscopy
National Category
Chemical Sciences
Identifiers
urn:nbn:se:liu:diva-122776 (URN)10.1002/chem.201502999 (DOI)000363332200011 ()26388448 (PubMedID)
Note

Funding Agencies|Swedish Foundation for Strategic Research; Erling Persson foundation; Alzheimers Disease Research Center (NIH) [AGO 5131]; ERC from the European Research Council; Swedish e-Science Research Center (SeRC); Swedish Research Council [621-2014-4646]

Available from: 2015-11-23 Created: 2015-11-23 Last updated: 2017-12-01
Lilledahl, M. B., Gustafsson, H., Gunnar Ellingsen, P., Zachrisson, H., Hallbeck, M., Stenhjem Hagen, V., . . . Lindgren, M. (2015). Combined imaging of oxidative stress and microscopic structure reveals new features in human atherosclerotic plaques. Journal of Biomedical Optics, 20(2), 020503
Open this publication in new window or tab >>Combined imaging of oxidative stress and microscopic structure reveals new features in human atherosclerotic plaques
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2015 (English)In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 20, no 2, p. 020503-Article in journal (Refereed) Published
Abstract [en]

Human atherosclerotic samples collected by carotid endarterectomy were investigated using electronic paramagnetic resonance imaging (EPRI) for visualization of reactive oxygen species, and nonlinear optical microscopy (NLOM) to study structural features. Regions of strong EPRI signal, indicating a higher concentration of reactive oxygen species and increased inflammation, were found to colocalize with regions dense in cholesterol crystals as revealed by NLOM.

Place, publisher, year, edition, pages
Society of Photo-optical Instrumentation Engineers (SPIE), 2015
Keywords
atherosclerosis; electronic paramagnetic resonance imaging; polarimetry; nonlinear optical microscopy
National Category
Clinical Medicine Chemical Sciences Cell and Molecular Biology
Identifiers
urn:nbn:se:liu:diva-116839 (URN)10.1117/1.JBO.20.2.020503 (DOI)000350462900003 ()25714991 (PubMedID)
Note

Funding Agencies|Swedish Research Council [diarienr 2009-5430]

Available from: 2015-04-07 Created: 2015-04-07 Last updated: 2019-10-14
Lunden, H., Liotta, A., Chateau, D., Lerouge, F., Chaput, F., Parola, S., . . . Lopes, C. (2015). Dispersion and self-orientation of gold nanoparticles in sol-gel hybrid silica - optical transmission properties. Journal of Materials Chemistry C, 3(5), 1026-1034
Open this publication in new window or tab >>Dispersion and self-orientation of gold nanoparticles in sol-gel hybrid silica - optical transmission properties
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2015 (English)In: Journal of Materials Chemistry C, ISSN 2050-7526, E-ISSN 2050-7534, Vol. 3, no 5, p. 1026-1034Article in journal (Refereed) Published
Abstract [en]

Silica-based hybrid materials doped with gold nanoparticles (AuNPs) of different shapes were prepared with an adapted sol-gel technology (using MTEOS) and polished to high optical quality. Both spherical (23 and 45 nm in diameter) and bipyramidal (36, 50 and 78 nm in length) AuNPs were prepared and used as dopants. The AuNPs were functionalized with a novel silicone polymer for compatibilization with the sol-gel medium. The glass materials showed well defined localized surface plasmon resonance (SPR) absorbance from the visible to NIR. No redshifts in the spectra, due to the increase in doping concentration, were observed in the glasses, proving that no or very small SPR coupling effects occur. Spectroscopic Muller Matrix Ellipsometry showed that the shorter bipyramidal AuNPs (36 and 50 nm in length) have a clear preferred orientation in the MTEOS matrix, i.e. a tendency to be oriented with their long axis in the plane parallel to the glass surfaces. Dispersions of AuNPs have proven to be good optical power limiters that depend on particle size and geometry. The solid-state glass materials showed good optical power limiting at 532 nm for nanosecond pulses, which did not depend on the size or geometry of the AuNPs. In contrast to the observation at 532 nm, at 600 nm no optical limiting effect was observed. In these solids, as for dispersions of AuNPs, the optical limiting response is caused by scattering.

Place, publisher, year, edition, pages
Royal Society of Chemistry, 2015
National Category
Physical Chemistry
Identifiers
urn:nbn:se:liu:diva-114589 (URN)10.1039/c4tc02353f (DOI)000348300300017 ()
Note

Funding Agencies|Swedish Armed Forces; EOARD [FA8655-12-12106]; AFRL [FA8655-12-12106]

Available from: 2015-02-27 Created: 2015-02-26 Last updated: 2019-04-29
Gustafsson, H., Hallbeck, M., Lindgren, M., Kolbun, N., Jonson, M., Engström, M., . . . Zachrisson, H. (2015). Visualization of oxidative stress in ex vivo biopsies using electron paramagnetic resonance imaging. Magnetic Resonance in Medicine, 73(4), 1682-1691
Open this publication in new window or tab >>Visualization of oxidative stress in ex vivo biopsies using electron paramagnetic resonance imaging
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2015 (English)In: Magnetic Resonance in Medicine, ISSN 0740-3194, E-ISSN 1522-2594, Vol. 73, no 4, p. 1682-1691Article in journal (Refereed) Published
Abstract [en]

PURPOSE: The purpose of this study was to develop an X-Band electron paramagnetic resonance imaging protocol for visualization of oxidative stress in biopsies.

METHODS: The developed electron paramagnetic resonance imaging protocol was based on spin trapping with the cyclic hydroxylamine spin probe 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine and X-Band EPR imaging. Computer software was developed for deconvolution and back-projection of the EPR image. A phantom containing radicals of known spatial characteristic was used for evaluation of the developed protocol. As a demonstration of the technique electron paramagnetic resonance imaging of oxidative stress was performed in six sections of atherosclerotic plaques. Histopathological analyses were performed on adjoining sections.

RESULTS: The developed computer software for deconvolution and back-projection of the EPR images could accurately reproduce the shape of a phantom of known spatial distribution of radicals. The developed protocol could successfully be used to image oxidative stress in six sections of the three ex vivo atherosclerotic plaques.

CONCLUSIONS: We have shown that oxidative stress can be imaged using a combination of spin trapping with the cyclic hydroxylamine spin probe cyclic hydroxylamine spin probe 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine and X-Band EPR imaging. A thorough and systematic evaluation on different types of biopsies must be performed in the future to validate the proposed technique. Magn Reson Med, 2014.

National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-113407 (URN)10.1002/mrm.25267 (DOI)000351685900035 ()24753234 (PubMedID)
Available from: 2015-01-19 Created: 2015-01-19 Last updated: 2019-10-14
Berg, K., Ericsson, M., Lindgren, M. & Gustafsson, H. (2014). A High Precision Method for Quantitative Measurements of Reactive Oxygen Species in Frozen Biopsies. PLoS ONE, 9(3)
Open this publication in new window or tab >>A High Precision Method for Quantitative Measurements of Reactive Oxygen Species in Frozen Biopsies
2014 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 3Article in journal (Refereed) Published
Abstract [en]

Objective

An electron paramagnetic resonance (EPR) technique using the spin probe cyclic hydroxylamine 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetr​amethylpyrrolidine(CMH) was introduced as a versatile method for high precision quantification of reactive oxygen species, including the superoxide radical in frozen biological samples such as cell suspensions, blood or biopsies.

Materials and Methods

Loss of measurement precision and accuracy due to variations in sample size and shape were minimized by assembling the sample in a well-defined volume. Measurement was carried out at low temperature (150 K) using a nitrogen flow Dewar. The signal intensity was measured from the EPR 1st derivative amplitude, and related to a sample, 3-carboxy-proxyl (CP•) with known spin concentration.

Results

The absolute spin concentration could be quantified with a precision and accuracy better than ±10 µM (k = 1). The spin concentration of samples stored at −80°C could be reproduced after 6 months of storage well within the same error estimate.

Conclusion

The absolute spin concentration in wet biological samples such as biopsies, water solutions and cell cultures could be quantified with higher precision and accuracy than normally achievable using common techniques such as flat cells, tissue cells and various capillary tubes. In addition; biological samples could be collected and stored for future incubation with spin probe, and also further stored up to at least six months before EPR analysis, without loss of signal intensity. This opens for the possibility to store and transport incubated biological samples with known accuracy of the spin concentration over time.

Place, publisher, year, edition, pages
San Francisco: Public Library of Science, 2014
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-105262 (URN)10.1371/journal.pone.0090964 (DOI)000332483600116 ()24603936 (PubMedID)
Available from: 2014-03-14 Created: 2014-03-14 Last updated: 2017-12-05Bibliographically approved
Simon, R., Bäck, M., Shirani, H., Lindgren, M. & Nilsson, P. R. (2014). pH-dependent optical transitions in anionic pentameric oligothiophenes.
Open this publication in new window or tab >>pH-dependent optical transitions in anionic pentameric oligothiophenes
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2014 (English)Manuscript (preprint) (Other academic)
Abstract [en]

Understanding the photo-physical processes in fluorescent probes are essential as such dyes are widely utilized in molecular biology. Here we report the pH-dependent optical transitions of a library of anionic pentameric luminescent conjugated oligothiophenes (LCOs) that have been used for fluorescent identification of protein aggregates, the pathological hallmark of many devastating diseases. Absorption-, excitation- and emission spectra were recorded for all LCOs in different buffers with a pH range from 3.5 to 7. p-FTAA, a LCO having a central core consisting of a trimeric thiophene  building block with head-to-head acetic acid functionalization as well as terminal carboxyl groups extending the pentameric thiophene backbone, displayed pH/dependent optical characteristics correlating to a non-planar to planar transition of the conjugated backbone as well as aggregation between adjacent thiophene chain upon protonation of the  acetic acid side chains. In contrast, chemically related analogues to p-FTAA lacking the  terminal carboxyl groups extending the pentameric thiophene backbone or the conformational ability to undergo a non/planar to planar transition of the  conjugated backbone, displayed different optical characteristics compared to p-FTAA. Overall these studies highlighted that minor chemical alteration of LCOs can result in major difference in the optical characteristics obtained from the dyes and the results might aid in designing novel LCOs that have  superior optical performance as amyloid ligands.

National Category
Chemical Sciences
Identifiers
urn:nbn:se:liu:diva-111656 (URN)
Available from: 2014-10-28 Created: 2014-10-28 Last updated: 2014-10-28Bibliographically approved
Sjöqvist, J., Maria, J., Simon, R., Linares, M., Norman, P., Nilsson, P. & Lindgren, M. (2014). Toward a molecular understanding of the detection of amyloid proteins with flexible conjugated oligothiophenes. Journal of Physical Chemistry A, 118(42), 9820-9827
Open this publication in new window or tab >>Toward a molecular understanding of the detection of amyloid proteins with flexible conjugated oligothiophenes
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2014 (English)In: Journal of Physical Chemistry A, ISSN 1089-5639, E-ISSN 1520-5215, Vol. 118, no 42, p. 9820-9827Article in journal (Refereed) Published
Abstract [en]

Molecular and electronic structures and optical absorption properties of oligothiophenes used for spectral assignment of amyloid deposits have been investigated for a family of probes known as luminescent conjugated oligothiophenes (LCOs). Theoretical absorption spectra have been determined using conformational averaging, combining classical molecular dynamics (MD) simulations with quantum mechanical/molecular mechanics (QM/MM) time-dependent density functional theory (TD-DFT) spectrum calculations. Theoretical absorption spectra are in excellent agreement with experiments, showing average errors below 5 nm for absorption maxima. To couple observed properties to molecular structures, a measure of planarity is defined, revealing a strong correlation between the transition wavelength of the first and dominating electronically excited state and dihedral rotations. It is shown that from this correlation, predictions can be made of the absorption properties of probes based only on information from MD trajectories. We show experimentally that red shifts observed in the excitation maxima of LCOs when bound to amyloid protein aggregates are also evident in absorption spectra. We predict that these red shifts are due to conformational restriction of the LCO in a protein binding pocket, causing a planarization of the conjugated backbone. On the basis of our studies of planarity, it is shown that such shifts are both possible and realistic.

Place, publisher, year, edition, pages
American Chemical Society (ACS), 2014
Keywords
UV/vis absorption spectra, density functional theory, QM/MM, molecular dynamics
National Category
Theoretical Chemistry Organic Chemistry
Identifiers
urn:nbn:se:liu:diva-109095 (URN)10.1021/jp506797j (DOI)000343741100004 ()
Note

At the time for thesis presentation publication was in status: Manuscript

Funding agencies: We acknowledge financial support from the Swedish Research Council (Grant No. 621-2010-5014) as well as a grant for computing time at the National Supercomputer Centre (NSC), Sweden. M.L. thanks the Swedish e-Science Research Center (SeRC) for financial support. Our work is supported by the Swedish Foundation for Strategic Research (K.P.R.N., R.A.S.). K.P.R.N. is financed by an ERC Starting Independent Researcher Grant (Project: MUMID) from the European Research Council. R.A.S. is enrolled in the doctoral program Forum Scientum. M.L. is grateful to Linkoping University for a guest professorship. Parts of this work were supported by the LUPAS project supported by the EU FP7 program.

Available from: 2014-08-11 Created: 2014-08-07 Last updated: 2017-12-05Bibliographically approved
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