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Preparation and Application of Functionalized Protein Fibrils
Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, Faculty of Science & Engineering.
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Many proteins have an innate ability to self-assemble into fibrous structures known as amyloid fibrils. From a material science perspective, fibrils have several interesting characteristics, including a high stability, a distinct shape and tunable surface properties. Such structures can be given additional properties through functionalization by other compounds such as fluorophores. Combination of fibrils with a function yielding compound can be achieved in several ways. Covalent bond attachment is specific, but cumbersome. External surface adhesion is nonspecific, but simple. However, in addition, internal non-covalent functionalization is possible. In this thesis, particular emphasis is put on internal functionalization of fibrils; by co-grinding fibril forming proteins with a hydrophobic molecule, a protein-hydrophobic compound molecule composite can be created that retains the proteins innate ability to form fibrils. Subsequently formed fibrils will thus have the structural properties of the protein fibril as well as the properties of the incorporated compound. The functionalization procedures used throughout this thesis are applicable for a wide range of chromophores commonly used for organic electronics and photonics. The methods developed and the prepared materials are useful for applications within optoelectronics as well as biomedicine.

Regardless of the methodology of functionalization, using functionalized fibrils in a controlled fashion for material design requires an intimate understanding of the formation process and knowledge of the tools available to control not only the formation but also any subsequent macroscale assembly of fibrils. The development and application of such tools are described in several of the papers included in this thesis. With the required knowledge in hand, the possible influence of fibrils on the functionalizing agents, and vice versa, can be probed. The characteristic traits of the functionalized fibril can be customized and the resulting material can be organized and steered towards a specific shape and form. This thesis describes how control over the process of formation, functionalization and organization of functionalized fibrils can be utilized to influence the hierarchical assembly of fibrils – ranging from spherical structures to  spirals; the function – fluorescent or conducting; and macroscopic properties – optical birefringence and specific arrangement of functionalized fibrils in the solid state. In conclusion, the use of amyloid fibrils in material science has great potential. Herein is presented a possible route towards a fully bottom up approach ranging from the nanoscale to the macroscale.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2015. , 70 p.
Series
Linköping Studies in Science and Technology. Dissertations, ISSN 0345-7524 ; 1695
National Category
Cell and Molecular Biology Physical Chemistry Physical Chemistry
Identifiers
URN: urn:nbn:se:liu:diva-121022ISBN: 978-91-7685-978-0 (print)OAI: oai:DiVA.org:liu-121022DiVA: diva2:850858
Public defence
2015-09-11, Planck, Fysikhuset, Campus Valla, Linköping, 10:15 (English)
Opponent
Supervisors
Available from: 2015-09-02 Created: 2015-09-02 Last updated: 2015-09-02Bibliographically approved
List of papers
1. Controlling Amyloid Fibril Formation by Partial Stirring
Open this publication in new window or tab >>Controlling Amyloid Fibril Formation by Partial Stirring
2016 (English)In: Biopolymers, ISSN 0006-3525, E-ISSN 1097-0282, Vol. 105, no 5, 249-259 p.Article in journal (Refereed) Published
Abstract [en]

Many proteins undergoes self-assembly into fibrillar structures known as amyloid fibrils. During the self-assembly process related structures, known as spherulites, can be formed. Herein we report a facile method where the balance between amyloid fibrils and spherulites can be controlled by stirring of the reaction mixture during the initial stages of the self-assembly process. Moreover, we report how this methodology can be used to prepare non-covalently functionalized amyloid fibrils. By stirring the reaction mixture continuously or for a limited time during the lag phase the fibril length, and hence the propensity to form liquid crystalline phases, can be influenced. This phenomena is utilized by preparing films consisting of aligned protein fibrils incorporating the laser dye Nile red. The resulting films display polarized Nile red fluorescence.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2016
National Category
Organic Chemistry Biomaterials Science
Identifiers
urn:nbn:se:liu:diva-121017 (URN)10.1002/bip.22803 (DOI)000371690100001 ()
Note

Funding agencies:  Swedish Government [2009-00971]; Knut and Alice Wallenberg foundation

Vid tiden för disputation förelåg publikationen endast som manuskript

Available from: 2015-09-02 Created: 2015-09-02 Last updated: 2016-04-07Bibliographically approved
2. Amyloid fibrils as dispersing agents for oligothiophenes: control of photophysical properties through nanoscale templating and flow induced fibril alignment
Open this publication in new window or tab >>Amyloid fibrils as dispersing agents for oligothiophenes: control of photophysical properties through nanoscale templating and flow induced fibril alignment
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2014 (English)In: Journal of Materials Chemistry C, ISSN 2050-7526, Vol. 2, no 37, 7811-7822 p.Article in journal (Refereed) Published
Abstract [en]

Herein we report that protein fibrils formed from aggregated proteins, so called amyloid fibrils, serve as an excellent dispersing agent for hydrophobic oligothiophenes such as alpha-sexithiophene (6T). Furthermore, the protein fibrils are capable of orienting 6T along the fibril long axis, as demonstrated by flow-aligned linear dichroism spectroscopy and polarized fluorescence microscopy. The materials are prepared by solid state mixing of 6T with a protein capable of self-assembly. This results in a water soluble composite material that upon heating in aqueous acid undergoes self-assembly into protein fibrils non-covalently functionalized with 6T, with a typical diameter of 5-10 nm and lengths in the micrometre range. The resulting aqueous fibril dispersions are a readily available source of oligothiophenes that can be processed from aqueous solvent, and we demonstrate the fabrication of macroscopic structures consisting of aligned 6T functionalized protein fibrils. Due to the fibril induced ordering of 6T these structures exhibit polarized light emission.

Place, publisher, year, edition, pages
Royal Society of Chemistry, 2014
National Category
Biological Sciences
Identifiers
urn:nbn:se:liu:diva-111311 (URN)10.1039/c4tc00692e (DOI)000341458000013 ()
Note

Funding Agencies|Swedish Research Council [20114324]; Swedish Strategic Research Foundation (SSF); Knut and Alice Wallenberg foundation through a Wallenberg Scholar grant; Chalmers Area of Advance in Nanoscience and Nanotechnology; Swedish Government Strategic Research Area in Materials Science on Functional Materials at Linkoping University (Faculty Grant SFO-Mat-LiU) [2009-00971]

Available from: 2014-10-14 Created: 2014-10-14 Last updated: 2015-09-02
3. Development and Application of Methodology for Rapid Screening of Potential Amyloid Probes
Open this publication in new window or tab >>Development and Application of Methodology for Rapid Screening of Potential Amyloid Probes
2014 (English)In: ACS COMBINATORIAL SCIENCE, ISSN 2156-8952, Vol. 16, no 12, 721-729 p.Article in journal (Refereed) Published
Abstract [en]

Herein, we demonstrate that it is possible to rapidly screen hydrophobic fluorescent aromatic molecules with regards to their properties as amyloid probes. By grinding the hydrophobic molecule with the amyloidogenic protein insulin, we obtained a water-soluble composite material. When this material is dissolved and exposed to conditions promoting amyloid formation, the protein aggregates into amyloid fibrils incorporating the hydrophobic molecule. As a result, changes in the fluorescence spectra of the hydrophobic molecule can be correlated to the formation of amyloid fibrils, and the suitability of the hydrophobic molecular skeleton as an amyloid probe can thus be assessed. As a result, we discovered two new amyloid probes, of which one is the well-known laser dye DCM. The grinding method can also be used for rapid preparation of novel composite materials between dyes and proteins, which can be used in materials science applications such as organic electronics and photonics.

Place, publisher, year, edition, pages
ACS Publications, 2014
Keyword
amyloid probes; rapid screening; fluorescent; aromatic molecules; laser dye DCM
National Category
Biological Sciences
Identifiers
urn:nbn:se:liu:diva-113169 (URN)10.1021/co5001212 (DOI)000346114600009 ()25383488 (PubMedID)
Note

Funding Agencies|Swedish Government Strategic Research Area in Materials Science on Functional Materials at Linkoping University [2009-00971]; Knut and Alice Wallenberg Foundation

Available from: 2015-01-14 Created: 2015-01-12 Last updated: 2015-09-02
4. Tuning the aqueous self-assembly process of insulin by a hydrophobic additive
Open this publication in new window or tab >>Tuning the aqueous self-assembly process of insulin by a hydrophobic additive
2015 (English)In: RSC ADVANCES, ISSN 2046-2069, Vol. 5, no 112, 92254-92262 p.Article in journal (Refereed) Published
Abstract [en]

Biomolecular self-assembly is an efficient way of preparing soft-matter based materials. Herein we report a novel method, based on the use of insoluble additives in aqueous media, for influencing the self-assembly process. Due to their low solubility, the use of hydrophobic additives in aqueous media is problematic; however, by mixing the additive with the biomolecule in the solid state, prior to solvation, this problem can be circumvented. In the investigated self-assembly system, where bovine insulin self-assembles into spherical structures, the inclusion of the hydrophobic material α-sexithiophene (6T) results in significant changes in the self-assembly process. Under our reaction conditions, in the case of materials prepared from insulin-only the growth of spherulites typically stops at a diameter of 150μm. However, by adding 2 weight % of hydrophobic material, spherulite growth continues up to diameters in the mm-range. The spherulites incorporate 6T and are thus fluorescent. The method reported herein should be of interest to all scientists working in the field of self-assembly as the flexible materials preparation, based simply on co-grinding of commercially available materials, adds another option to influence the structure and properties of products formed by  self-assembly reactions.

Place, publisher, year, edition, pages
Royal Society of Chemistry, 2015
National Category
Organic Chemistry Biomaterials Science
Identifiers
urn:nbn:se:liu:diva-121018 (URN)10.1039/c5ra16144d (DOI)000364032500040 ()
Note

Funding agencies: Swedish Government Strategic Research Area in Materials Science on Functional Materials at Linkoping University (Faculty Grant SFO-Mat-LiU) [2009-00971]; Knut and Alice Wallenberg foundation

Available from: 2015-09-02 Created: 2015-09-02 Last updated: 2015-12-03
5. Convection Induced Air-Water Interface Assembly of Amyloid Fibrils
Open this publication in new window or tab >>Convection Induced Air-Water Interface Assembly of Amyloid Fibrils
(English)Manuscript (preprint) (Other academic)
Abstract [en]

We report that hydrophobically modified amyloid fibrils form macroscopic films at the air-water interface. The hydrophobically modified fibrils are prepared in a two step process. First bovine insulin is ground with a hydrophobic compound. The resulting material is dissolved in acidic water and heated to induce assembly into fibrils incorporating the hydrophobic compounds. Upon dilution followed by asymmetric heating, resulting in convection flow, the fibrills form highly ordered films with thicknesses from 80 nm and up. The thickness of the film can be controlled by the fibril concentration and/or reaction time. The films contain anisotropic domains spanning several square centimeters. In addition, the films contains ordered assemblies of dyes that display emission of polarized light.

National Category
Organic Chemistry Biomaterials Science
Identifiers
urn:nbn:se:liu:diva-121019 (URN)
Available from: 2015-09-02 Created: 2015-09-02 Last updated: 2015-09-02
6. Protein nanowires with conductive properties
Open this publication in new window or tab >>Protein nanowires with conductive properties
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2015 (English)In: Journal of Materials Chemistry C, ISSN 2050-7526, Vol. 3, no 25, 6499-6504 p.Article in journal (Refereed) Published
Abstract [en]

Herein we report on the investigation of self-assembled protein nanofibrils functionalized with metallic organic compounds. We have characterized the electronic behaviour of individual nanowires using conductive atomic force microscopy. In order to follow the self assembly process we have incorporated fluorescent molecules into the protein and used the energy transfer between the internalized dye and the metallic coating to probe the binding of the polyelectrolyte to the fibril.

Place, publisher, year, edition, pages
Royal Society of Chemistry, 2015
National Category
Biological Sciences
Identifiers
urn:nbn:se:liu:diva-120179 (URN)10.1039/c5tc00896d (DOI)000356529100010 ()
Note

Funding Agencies|Knut and Alice Wallenberg Foundation through a Wallenberg Scholar grant

Available from: 2015-07-13 Created: 2015-07-13 Last updated: 2015-09-02
7. PEDOT-S coated protein fibril microhelices
Open this publication in new window or tab >>PEDOT-S coated protein fibril microhelices
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

We show here the preparation and characterization of micrometer sized conductive helices. We utilize protein fibrils as structural templates to create chiral helices with either right or left handed helicity. The helices are coated with the conductive polymer alkoxysulfonate poly(ethylenedioxythiophene) (PEDOT-S) to create micrometer sized conductive helices. The coating acts as a stabilizer for the template structure, facilitates the preparation of solid state films and shows significant conductivity. The helices have been investigated using Circular Dichroism (CD) and scanning electron microscopy (SEM) and the conductivity have been measured for solid state films.

National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:liu:diva-121020 (URN)
Available from: 2015-09-02 Created: 2015-09-02 Last updated: 2015-09-02Bibliographically approved

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