DESCRIPTION: The goal of the proposed experiments is to address two broad questions. How do non-muscle tissue cells regulate the contractile forces they exert on each other and on the extracellular matrices in which they are embedded? To what extent and how can these cells sense external forces exerted on them and respond biochemically and mechanically. Six goals are proposed : (1) to determine the contribution of different signaling pathways to the activation of myosin and the exertion of contractile force; (2) to determine how myosin activation results from disruption of the microtubule network; (3) to determine the pathway by which phospholipase C delta1 contributes to generation of contractile force in fibroblasts; (4) to determine the roles of selected actin filament capping proteins in controlling the stiffness of the actin cytoskeleton; (5) to determine how adhesion to the ECM contributes to development of tissues and the exertion of force; and (6) to determine whether the exertion of force on cells via integrin-ligand interactions has important regulatory functions.