Integrin-fibronectin interactions at the cell-material interface: initial integrin binding and signaling

Integrin receptors mediate cell adhesion to extracellular matrices and prov ide signals that direct proliferation and differentiation. Integrin binding involves receptor-ligand interactions at the cell-substrate interface and assembly and reorganization of structural and signaling elements at the cyt oplasmic face. Using a cross-linking/extraction/reversal method to quantify bound integrins, we demonstrate that the density of alpha(5)beta(1) integr in-fibronectin bonds increases linearly with ligand density, as predicted b y simple receptor-ligand equilibrium. This linear relationship is consisten t with linear increases in cell adhesion strength with receptor and ligand surface densities. Furthermore, we show that phosphorylation of FAK, a tyro sine kinase involved in early integrin-mediated signaling, increases linear ly with the number of integrin-Fn bonds. These linear relationships suggest the absence of cooperative effects in the initial stages of mechanical cou pling and adhesion-mediated signaling. (C) 1999 Elsevier Science Ltd. All r ights reserved.