Design of novel biomimetic peptide-amphiphiles for functional biomaterials

Anastasia Mardilovich, Jennifer Craig, Ashish Garg, Matthew McCammon, Efrosini Kokkoli

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

Cell-matrix adhesion mediated by integrins regulates several aspects of cell behavior and is critical to cellular responses on biomaterial surfaces. While many integrins recognize a short Arg-Gly-Asp (RGD) motif present in several extracellular matrix proteins, integrin α5β 1 requires a synergy sequence, Pro-His-Ser-Arg-Asn (PHSRN), present in the 9th type III domain of fibronectin (FN), in addition to its primary recognition sequence Gly-Arg-Gly-Asp-Ser-Pro (GRGDSP), present in the 10th type III domain of FN, for enhanced specificity and higher affinity binding. The focus of this work was to engineer α5β1 integrin-specific bioadhesive interfaces using supported bilayer membranes constructed from peptideamphiphiles that mimic the adhesion domain of fibronectin. Novel peptide-amphiphiles were designed that contain both the GRGDSP and PHSRN sequences in a single peptide formulation, separated by a spacer. Cell adhesion, blocking assays, and confocal microscopy were used to evaluate human umbilical vein endothelial cell (HUVEC) response on biomimetic interfaces. Cell adhesion to the new peptides was found to be comparable to the one observed on the FN-coated surfaces both initially (1 and 4 hours of incubation) and at longer times, whereas surfaces with GRGDSP alone failed to sustain cell adhesion by 24 hours. The effect of the PHSRN, the spacer length between the GRGDSP and PHSRN in the new peptides, and incubation time on HUVEC adhesion to the new FN-mimetic peptide will be discussed.

Original languageEnglish (US)
Title of host publication05AIChE
Subtitle of host publication2005 AIChE Annual Meeting and Fall Showcase, Conference Proceedings
Number of pages1
StatePublished - Dec 1 2005
Event05AIChE: 2005 AIChE Annual Meeting and Fall Showcase - Cincinnati, OH, United States
Duration: Oct 30 2005Nov 4 2005

Other

Other05AIChE: 2005 AIChE Annual Meeting and Fall Showcase
CountryUnited States
CityCincinnati, OH
Period10/30/0511/4/05

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