Dynamic heterodimer-functionalized surfaces for endothelial cell adhesion

Biomaterials. 2005 Aug;26(23):4757-66. doi: 10.1016/j.biomaterials.2004.11.060.

Abstract

The functionalization of hydrogels for receptor-mediated cell adhesion is one approach for targeted cell and tissue engineering applications. In this study, polyacrylamide gel surfaces were functionalized with specific cell adhesion ligands via the self-assembly of a peptide-based heterodimer. The system was comprised of a cysteine-terminated monomer, A (MW approximately 5400), grafted to the polyacrylamide gels and a complementary ligand presenting monomer, B(X) (MW approximately 5800) that was designed to heterodimerize with A. Two ligand presenting monomers were synthesized: one presenting the RGDS ligand, B(D), for receptor-mediated cell adhesion, and the other, a control monomer presenting the nonadhesive RGES ligand, B(E). Assembly of the peptide pair A-B(X) by association of the monomers into a coiled coil was verified by circular dichroism in solution. Binding studies were conducted to determine the dissociation constant of the pair A-B(X), which was found to be K(D) approximately 10(-8) m. Polyacrylamide gels functionalized with A-B(X) heterodimers were evaluated for cell adhesion using bovine aortic endothelial cells (BAECs). Endothelial cells cultured on the A-B(D) functionalized surfaces demonstrated typical cell morphologies and expected spreading behavior as a function of the density of RGDS ligand, calculated as the amount of B(D) associated with grafted A on the surface of the gels. In contrast, A-B(E) linked surfaces supported no cell adhesion. The adhesion of the substrate was dynamically altered through the reassembly of A-B(X) dimers as B(D) molecules in the solution replaced B(E) molecules at the substrate. The molecular constructs described here demonstrate the potential to design a broad family of switchable peptides that impart the dynamic control of biofunctionality at an interface, which would be useful for precise manipulation of cell physiology.

Publication types

  • Evaluation Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adsorption
  • Animals
  • Cattle
  • Cell Adhesion / drug effects
  • Cell Adhesion / physiology
  • Cell Movement / drug effects
  • Cell Size / drug effects
  • Cells, Cultured
  • Coated Materials, Biocompatible / chemistry*
  • Coated Materials, Biocompatible / pharmacology*
  • Dimerization
  • Endothelial Cells / cytology*
  • Endothelial Cells / drug effects
  • Endothelial Cells / physiology*
  • Materials Testing
  • Oligopeptides / chemistry*
  • Oligopeptides / pharmacology*
  • Protein Binding
  • Surface Properties
  • Tissue Engineering / methods*

Substances

  • Coated Materials, Biocompatible
  • Oligopeptides
  • arginyl-glycyl-aspartyl-serine