Physical state of the extracellular matrix regulates the structure and molecular composition of cell-matrix adhesions

This study establishes that the physical state of the extracellular matrix can regulate integrin-mediated cytoskeletal assembly and tyrosine phosphory lation to generate two distinct types of cell-matrix adhesions. In primary fibroblasts, alpha(5)beta(1) integrin associates mainly with fibronectin fi brils and forms adhesions structurally distinct from focal contacts, indepe ndent of actomyosin-mediated cell contractility. These "fibrillar adhesions " are enriched in tensin, but contain low levels of the typical focal conta ct components paxillin, vinculin, and tyrosine-phosphorylated proteins. How ever, when the fibronectin is covalently linked to the substrate, alpha(5)b eta(1) integrin forms highly tyrosine-phosphorylated, "classical" focal con tacts containing high levels of paxillin and vinculin. These experiments in dicate that the physical state of the matrix, not just its molecular compos ition, is a critical factor in defining cytoskeletal organization and phosp horylation at adhesion sites. We propose that molecular organization of adh esion sites is controlled by at least two mechanisms: 1) specific integrins associate with their ligands in transmembrane complexes with appropriate c ytoplasmic anchor proteins (e.g., fibronectin-alpha(5)beta(1) integrin-tens in complexes), and 2) physical properties (e.g., rigidity) of the extracell ular matrix regulate local tension at adhesion sites and activate local tyr osine phosphorylation, recruiting a variety of plaque molecules to these si tes. These mechanisms generate structurally and functionally distinct types of matrix adhesions in fibroblasts.