Positively and negatively modulating cell adhesion to type I collagen via peptide grafting.
The biophysical interactions between cells and type I collagen are controlled by the level of cell adhesion, which is dictated primarily by the density of ligands on collagen and the density of integrin receptors on cells. The native adhesivity of collagen was modulated by covalently grafting glycine-arginine-glycine-aspartic acid-serine (GRGDS), which includes the bioactive RGD sequence, or glycine-arginine-aspartic acid-glycine-serine (GRDGS), which includes the scrambled RDG sequence, to collagen with the hetero-bifunctional coupling agent 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide. The peptide-grafted collagen self-assembled into a fibrillar gel with negligible changes in gel structure and rheology. Rat dermal fibroblasts (RDFs) and human smooth muscle cells demonstrated increased levels of adhesion on gels prepared from RGD-grafted collagen, and decreased levels of adhesion on RDG-grafted collagen. Both cell types demonstrated an increased ability to compact free-floating RGD-grafted collagen gels, and an impaired ability to compact RDG-grafted gels. RDF migration on and within collagen was increased with RDG-grafted collagen and decreased with RGD-grafted collagen, and dose-response experiments indicated a biphasic response of RDF migration to adhesion. Smooth muscle cells demonstrated similar, though not statistically significant, trends. The ability to both positively and negatively modulate cell adhesion to collagen increases the versatility of this natural biomaterial for regenerative therapies.
Monteiro
Gary A
GA
Department of Biomedical Engineering, The State University of New Jersey, Piscataway, New Jersey 08854, USA.
Fernandes
Anthony V
AV
Sundararaghavan
Harini G
HG
Shreiber
David I
DI
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D024042:Collagen Type I / Q000378:metabolism* / Q000494:pharmacology*; D055119:Elastic Modulus / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects*; D005782:Gels; D006801:Humans; D018613:Microscopy, Confocal; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000187:drug effects*; D009842:Oligopeptides / Q000378:metabolism / Q000494:pharmacology; D010455:Peptides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D051381:Rats
D024042:Collagen Type I; D005782:Gels; D009842:Oligopeptides; D010455:Peptides; C047981:arginyl-glycyl-aspartic acid