RGD peptides may only temporarily inhibit cell adhesion to fibronectin.

When human fibroblasts were cultured on fibronectin for 4 h in the presence of 0.5 mg/ml of the GRGDSP peptide derived from the fibronectin cell-binding site, they adhered and spread normally and organized talin and integrin alpha 5 and beta 1 subunits into focal adhesions. When the adherent cells were quantitated as a function of time, submaximal peptide concentrations were found to delay cell adhesion on fibronectin, but they had no effect on the maximum. When the cells were plated on vitronectin, however, even relatively low peptide concentrations lowered the maximal amount of cells adhering and abolished cell spreading. The results suggest a different mechanism for cell adhesion on fibronectin and vitronectin.