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Self-sorting heterodimeric coiled coil peptides with defined and tuneable self-assembly properties
Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
Nanyang Technology University, Singapore.
Linköping University, Department of Electrical Engineering, Vehicular Systems. Linköping University, The Institute of Technology.
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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. Vol. 5, no 14063
National Category
Physical Sciences Electrical Engineering, Electronic Engineering, Information Engineering
Identifiers
URN: urn:nbn:se:liu:diva-121739DOI: 10.1038/srep14063ISI: 000361177400001PubMedID: 26370878OAI: oai:DiVA.org:liu-121739DiVA: diva2:859365
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
In thesis
1. Tunable and modular assembly of polypeptides and polypeptide-hybrid biomaterials
Open this publication in new window or tab >>Tunable and modular assembly of polypeptides and polypeptide-hybrid biomaterials
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. 93 p.
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:nbn:se:liu:diva-132949 (URN)10.3384/diss.diva-132949 (DOI)9789176856277 (ISBN)
Public defence
2017-01-13, Planck, Fysikhuset, Campus Valla, Linköping, 09:15 (English)
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Available from: 2016-12-05 Created: 2016-12-05 Last updated: 2016-12-06Bibliographically approved

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Aronsson, ChristopherDånmark, StaffanÖberg, PerEnander, KarinAili, Daniel

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