n in tz

nce activation of downstream signaling. In addition, force generation by cells depends on a feedback mechanism integrin–cytoskeleton linkages, which increased in direct Review TRENDS in Cell Biology Vol.16 No.4 April 2006have yet to be identified.demonstrate that mechanical factors affect cellular functions. At the level of cell growth and viability, normal cells require a rigid substrate or internal cytoskeletal tension for growth, whereas transformed cells have lost this requirement [1,2]. ECM rigidity and shear flow can alter migration [3,4], tyrosine kinase activities [5–7], gene expression [8,9] and cellular differentiation [10,11] in various cell types. Force transducers involved in mechan-osensation are ion channels that convert mechanical force into an electrical or chemical signal [12]. However, the detailed mechanisms of force transduction in responses to the ECM during adhesion, migration or cell differentiation proportion to the applied stress. Although general changes in the cytoskeletal rigidity have been described as a result of external forces [19], adhesion site initiation and maturation occur locally where the forces are applied in fibroblasts [14,16,17,20–22] or in the direction of shear flow in endothelial cells [4]. Additional studies showed that forces affect integrin-dependent adhesion properties [23], linkage to the actin cytoskeleton [14] and recruit-ment and activation of signaling proteins [6]. Rigidity responses are difficult to understand because local, transient mechanical perturbations can be con-verted to distinct biochemical signals that have either limited or global effects on cellular functions. These(ECM) and cell–cell contacts are subjected to force fluctuations and adjust to changes in tension. Studiesand decompression. Therefore, cell–extracellular matrix cytoskeletal stiffening or the mechanical reinforcement ofbetween matrix rigidity or force generation and myosin contractility. Components of the force-sensing pathway are linked to the integrin–cytoskeleton complex at sites of force application and serve as scaffolds for signaling processes. Thus, early events in force detection are mechanically induced cytoskeletal changes that result in biochemical signals to mechanoresponsive pathways that then regulate cell form