liu.seSearch for publications in DiVA
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Tunable and modular assembly of polypeptides and polypeptide-hybrid biomaterials
Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

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

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

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

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

.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2016. , p. 93
Series
Linköping Studies in Science and Technology. Dissertations, ISSN 0345-7524 ; 1810
National Category
Atom and Molecular Physics and Optics Biomaterials Science Biochemistry and Molecular Biology Physical Chemistry Biophysics
Identifiers
URN: urn:nbn:se:liu:diva-132949DOI: 10.3384/diss.diva-132949ISBN: 9789176856277 (print)OAI: oai:DiVA.org:liu-132949DiVA, id: diva2:1052106
Public defence
2017-01-13, Planck, Fysikhuset, Campus Valla, Linköping, 09:15 (English)
Opponent
Supervisors
Available from: 2016-12-05 Created: 2016-12-05 Last updated: 2016-12-06Bibliographically approved
List of papers
1. Self-sorting heterodimeric coiled coil peptides with defined and tuneable self-assembly properties
Open this publication in new window or tab >>Self-sorting heterodimeric coiled coil peptides with defined and tuneable self-assembly properties
Show others...
2015 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, no 14063Article in journal (Refereed) Published
Abstract [en]

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

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

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

Available from: 2015-10-06 Created: 2015-10-05 Last updated: 2017-12-01
2. Tailoring Supramolecular Peptide-Poly(ethylene glycol) Hydrogels by Coiled Coil Self-Assembly and Self-Sorting
Open this publication in new window or tab >>Tailoring Supramolecular Peptide-Poly(ethylene glycol) Hydrogels by Coiled Coil Self-Assembly and Self-Sorting
2016 (English)In: Biomacromolecules, ISSN 1525-7797, E-ISSN 1526-4602, Vol. 17, no 6, p. 2260-2267Article in journal (Refereed) Published
Abstract [en]

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

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

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

Available from: 2016-07-12 Created: 2016-07-11 Last updated: 2017-11-28
3. Zinc-Triggered Hierarchical Self-Assembly of Fibrous Helix-Loop-Helix Peptide Superstructures for Controlled Encapsulation and Release
Open this publication in new window or tab >>Zinc-Triggered Hierarchical Self-Assembly of Fibrous Helix-Loop-Helix Peptide Superstructures for Controlled Encapsulation and Release
2016 (English)In: Macromolecules, ISSN 0024-9297, E-ISSN 1520-5835, Vol. 49, no 18, p. 6997-7003Article in journal (Refereed) Published
Abstract [en]

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

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

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

Available from: 2016-10-26 Created: 2016-10-21 Last updated: 2017-11-29

Open Access in DiVA

Tunable and modular assembly of polypeptides and polypeptide-hybrid biomaterials(50806 kB)138 downloads
File information
File name FULLTEXT01.pdfFile size 50806 kBChecksum SHA-512
ec15ce13388236b06eba94eb38cd2929ae39b3a78d8b44e8c2109e1f490289cda8ec2e71959a7c457263d8d7276fb57ea03d5702998f7ada2d8ce18a757a0e0f
Type fulltextMimetype application/pdf
omslag(3209 kB)24 downloads
File information
File name COVER01.pdfFile size 3209 kBChecksum SHA-512
ab1812db7577843af3818b523185c07d6ca2cbe9cd411ba0872e9be72b7f8a408cf42bca2ca3de7ea5ee3e5056649268fae938d96866d1612888e17f0e7556a9
Type coverMimetype application/pdf

Other links

Publisher's full text

Search in DiVA

By author/editor
Aronsson, Christopher
By organisation
Molecular PhysicsFaculty of Science & Engineering
Atom and Molecular Physics and OpticsBiomaterials ScienceBiochemistry and Molecular BiologyPhysical ChemistryBiophysics

Search outside of DiVA

GoogleGoogle Scholar
Total: 138 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
isbn
urn-nbn

Altmetric score

doi
isbn
urn-nbn
Total: 1322 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf