PUBLICATION

The in vivo performance of an enzyme-assisted self-assembled peptide/protein hydrogel

Authors
Williams, R.J., Hall, T.E., Glattauer, V., White, J., Pasic, P.J., Sorensen, A.B., Waddington, L., McLean, K.M., Currie, P.D., and Hartley, P.G.
ID
ZDB-PUB-110519-10
Date
2011
Source
Biomaterials   32(22): 5304-5310 (Journal)
Registered Authors
Currie, Peter D., Hall, Thomas
Keywords
self assembly, peptide, animal model, hydrogel, ECM (extracellular matrix), laminin
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Fluorenes/chemistry
  • Hydrogels/chemical synthesis
  • Hydrogels/chemistry*
  • Laminin/genetics
  • Laminin/metabolism
  • Leucine/chemistry
  • Materials Testing
  • Molecular Structure
  • Nanofibers/chemistry
  • Nanofibers/ultrastructure
  • Peptides/chemistry*
  • Protein Conformation*
  • Proteins/chemistry*
  • Zebrafish/anatomy & histology
  • Zebrafish/genetics
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed
21531457 Full text @ Biomaterials
Abstract

We demonstrate the distribution of the important extracellular matrix protein laminin in a novel biomaterial consisting of a hydrogel underpinned by nanofibrillar networks. These are formed by the immobilised enzyme mediated self-assembly of fmoc-L3 (9-fluorenylmethoxycarbonyl-tri-leucine). The peptide assembly yields nanofibrils formed of β-sheets that are locked together via π-stacking interactions. This ordering allows the localisation of the peptide sidechains on the surface, creating a hydrophobic environment. This induces the formation of bundles of these nanofibrils producing a clear hydrogel. This mechanism enables the three dimensional distribution of laminin throughout the network via supramolecular interactions. These forces favour the formation and improve the order of the network itself, as observed by spectroscopic and mechanical testing. In order to test the stability and suitability of this class of material for in vivo applications, we utilise microinjection to deliver the biomaterial under fine spatial control into a dystrophic zebrafish model organism, which lacks laminin as a result of a genetic mutation. Using confocal and transmission electron microscopy, we confirm that the biomaterial remains stable structurally, and is confined spatially to the site of injection.

Genes / Markers
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping