Maleimide-thiol coupling of a bioactive peptide to an elastin-like protein polymer

• Type of Material: Article
• Authors: Swathi Ravi, Emory University; Venkatagiri Krishnamurthy, Emory University; Jeffrey M. Caves, Emory University; Carolyn A. Haller, Emory University; Elliot L. Chaikof, Emory University
• Language: English
• Date: 2012-02-01
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2011 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.actbio.2011.10.027
• Title of Journal or Parent Work: Acta Biomaterialia
• ISSN: 1742-7061
• Volume: 8
• Issue: 2
• Start Page: 627
• End Page: 635
• Keywords: Cell Movement; Animals; Microscopy, Confocal; Elastin; Oligopeptides; Maleimides; Cell Proliferation; Amino Acid Sequence; Humans; Peptides; Human Umbilical Vein Endothelial Cells; Sus scrofa; Cell Adhesion; Molecular Sequence Data; Biocompatible Materials; Sulfhydryl Compounds; Cells, Cultured; Hydrogel, Polyethylene Glycol Dimethacrylate; Mesenchymal Stem Cells
• Research Categories: Chemistry, Biochemistry; Biology, Cell; Engineering, Biomedical

Abstract

Recombinant elastin-like protein (ELP) polymers display several favorable characteristics for tissue repair and replacement as well as drug delivery applications. However, these materials are derived from peptide sequences that do not lend themselves to cell adhesion, migration, or proliferation. This report describes the chemoselective ligation of peptide linkers bearing the bioactive RGD sequence to the surface of ELP hydrogels. Initially, cystamine is conjugated to ELP, followed by the temperature-driven formation of elastomeric ELP hydrogels. Cystamine reduction produces reactive thiols that are coupled to the RGD peptide linker via a terminal maleimide group. Investigations into the behavior of endothelial cells and mesenchymal stem cells on the RGD-modified ELP hydrogel surface reveal significantly enhanced attachment, spreading, migration and proliferation. Attached endothelial cells display a quiescent phenotype.