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Conjugated polyelectrolytes: conformation-sensitive optical probes for detection of amyloid fibril formation
Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, The Institute of Technology.ORCID iD: 0000-0002-5582-140X
Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, The Institute of Technology.
Linköping University, Department of Physics, Chemistry and Biology, Biochemistry. Linköping University, The Institute of Technology.
Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, The Institute of Technology.
2005 (English)In: Biochemistry, ISSN 0006-2960, E-ISSN 1520-4995, Vol. 44, no 10, 3718-3724 p.Article in journal (Refereed) 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.

Place, publisher, year, edition, pages
2005. Vol. 44, no 10, 3718-3724 p.
National Category
Engineering and Technology
Identifiers
URN: urn:nbn:se:liu:diva-14599DOI: 10.1021/bi047402uOAI: oai:DiVA.org:liu-14599DiVA: diva2:23992
Available from: 2007-10-12 Created: 2007-10-12 Last updated: 2014-04-08
In thesis
1. Conjugated Polymers, Amyloid Detection and Assembly of Biomolecular Nanowires
Open this publication in new window or tab >>Conjugated Polymers, Amyloid Detection and Assembly of Biomolecular Nanowires
2007 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The research field of conjugated polymers has grown due to the optical and electronic properties of the material, useful in applications such as solar cells and printed electronics, but also in biosensors and for interactions with biomolecules. In this thesis conjugated polymers have been used in two related topics; to detect conformational changes in proteins and to assemble the polymers with biomolecules into nanowires.

Within biosensing, conjugated polymers have been used for detection of a wide range of biological events, such as DNA hybridization or enzymatic activity, utilizing both electronic and optical changes in the polymer. Here the focus has been to use the polymers as optical probes to discriminate between native and misfolded protein, as well as to follow the misfolding processes in vitro. The understanding and detection of protein misfolding, for example amyloid fibril formation, is a topic of growing importance. The misfolding process is strongly associated with several devastating diseases such as Alzheimer’s disease, Parkinson’s disease and Bovine Spongiform Encephalopathy (BSE). We have developed detection schemes for discrimination between proteins in the native or amyloid fibril state based on luminescent polythiophene derivatives. Through a synthesis strategy based on polymerization of trimer blocks rather than of monomers, polythiophene derivatives with higher optical signal specificity for amyloid-like fibrils were obtained.

Self-assembly of nanowires containing conjugated polymers is a route to generate structures of unique opto-electrical characteristics without the need for tedious topdown processes. Biomolecules can have nanowire geometries of extraordinary aspect ratio and functionalities. The DNA molecule is the most well known and exploited of these. In this thesis work the more stable amyloid fibril has been used as a template to organize conjugated polymers. Luminescent, semi-conducting, conjugated polymers have been incorporated in and assembled onto amyloid fibrils. Using luminescence quenching we have demonstrated that the conjugated material can retain the electro-activity after the incorporation process. Furthermore, the amyloid fibril/conjugated polymer hybrid structures can be organized on surfaces by the means of molecular combing and soft lithography.

In the process of generating self-assembled biomolecular nanowires functionalized with conjugated polymers, we have shown a new synthesis strategy for a water-soluble highly conducting polythiophene derivative. This material, PEDOT-S, has shown affinity for amyloid fibrils, but can also be very useful in conventional opto-electronic polymer-based devices.

Place, publisher, year, edition, pages
Institutionen för fysik, kemi och biologi, 2007
Series
Linköping Studies in Science and Technology. Dissertations, ISSN 0345-7524 ; 1117
Keyword
Conjugated Polymers, Amyloid Fibrils, Nanowires, Self-Assembly, Sensor, Amyloid Detection
National Category
Physical Sciences
Identifiers
urn:nbn:se:liu:diva-9577 (URN)978-91-85831-42-5 (ISBN)
Public defence
2007-09-04, Planck, Physics Building, Linköping University, Linköping, 10:15 (English)
Opponent
Supervisors
Available from: 2007-10-12 Created: 2007-10-12 Last updated: 2009-04-29
2. Conjugated polyelectrolytes: conformation sensitive optical probes for the recording of biological processes
Open this publication in new window or tab >>Conjugated polyelectrolytes: conformation sensitive optical probes for the recording of biological processes
2005 (English)Doctoral thesis, comprehensive summary (Other academic)
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.

Place, publisher, year, edition, pages
Linköping: Linköpings universitet, 2005. 61 p.
Series
Linköping Studies in Science and Technology. Dissertations, ISSN 0345-7524 ; 961
National Category
Natural Sciences
Identifiers
urn:nbn:se:liu:diva-30214 (URN)15709 (Local ID)91-85457-01-9 (ISBN)15709 (Archive number)15709 (OAI)
Public defence
2005-09-15, Planck, Fysikhuset, Linköpings universitet, Linköping, 13:15 (Swedish)
Opponent
Available from: 2009-10-09 Created: 2009-10-09 Last updated: 2014-04-08

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Nilsson, PeterHerland, AnnaHammarström, PerInganäs, Olle

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