liu.seSearch for publications in DiVA
Endre søk
RefereraExporteraLink to record
Permanent link

Direct link
Referera
Referensformat
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Self-sorting heterodimeric coiled coil peptides with defined and tuneable self-assembly properties
Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär fysik. Linköpings universitet, Tekniska fakulteten.ORCID-id: 0000-0001-7921-8915
Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär fysik. Linköpings universitet, Tekniska fakulteten.
Nanyang Technology University, Singapore.
Linköpings universitet, Institutionen för systemteknik, Fordonssystem. Linköpings universitet, Tekniska högskolan.
Vise andre og tillknytning
2015 (engelsk)Inngår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, nr 14063Artikkel i tidsskrift (Fagfellevurdert) 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.

sted, utgiver, år, opplag, sider
NATURE PUBLISHING GROUP , 2015. Vol. 5, nr 14063
HSV kategori
Identifikatorer
URN: urn:nbn:se:liu:diva-121739DOI: 10.1038/srep14063ISI: 000361177400001PubMedID: 26370878OAI: oai:DiVA.org:liu-121739DiVA, id: diva2:859365
Merknad

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

Tilgjengelig fra: 2015-10-06 Laget: 2015-10-05 Sist oppdatert: 2019-01-22
Inngår i avhandling
1. Tunable and modular assembly of polypeptides and polypeptide-hybrid biomaterials
Åpne denne publikasjonen i ny fane eller vindu >>Tunable and modular assembly of polypeptides and polypeptide-hybrid biomaterials
2016 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
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

.

sted, utgiver, år, opplag, sider
Linköping: Linköping University Electronic Press, 2016. s. 93
Serie
Linköping Studies in Science and Technology. Dissertations, ISSN 0345-7524 ; 1810
HSV kategori
Identifikatorer
urn:nbn:se:liu:diva-132949 (URN)10.3384/diss.diva-132949 (DOI)9789176856277 (ISBN)
Disputas
2017-01-13, Planck, Fysikhuset, Campus Valla, Linköping, 09:15 (engelsk)
Opponent
Veileder
Tilgjengelig fra: 2016-12-05 Laget: 2016-12-05 Sist oppdatert: 2019-10-29bibliografisk kontrollert

Open Access i DiVA

fulltext(926 kB)203 nedlastinger
Filinformasjon
Fil FULLTEXT01.pdfFilstørrelse 926 kBChecksum SHA-512
80cfd2131dc68bfafbc384c7231fb79656ffd403d211491bff8fe15dff096a7821413dddf584ea232c6cac9169fef8bf02ca3dcd5a3694a8e1590fe71ca44346
Type fulltextMimetype application/pdf

Andre lenker

Forlagets fulltekstPubMed

Personposter BETA

Aronsson, ChristopherDånmark, StaffanÖberg, PerEnander, KarinAili, Daniel

Søk i DiVA

Av forfatter/redaktør
Aronsson, ChristopherDånmark, StaffanÖberg, PerEnander, KarinAili, Daniel
Av organisasjonen
I samme tidsskrift
Scientific Reports

Søk utenfor DiVA

GoogleGoogle Scholar
Totalt: 203 nedlastinger
Antall nedlastinger er summen av alle nedlastinger av alle fulltekster. Det kan for eksempel være tidligere versjoner som er ikke lenger tilgjengelige

doi
pubmed
urn-nbn

Altmetric

doi
pubmed
urn-nbn
Totalt: 622 treff
RefereraExporteraLink to record
Permanent link

Direct link
Referera
Referensformat
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf