Role of integrins and focal adhesion kinase in the orientation of dermal fibroblasts exposed to cyclic strain.

Stretch is applied to skin under normal physiological conditions, for example pregnancy, or artificially using soft tissue expanders. Because cells are known to orient in response to the application of mechanical forces, the current studies were carried out to assess the effects of stretch on dermal fibroblast orientation and cell signalling. Dermal fibroblasts were seeded onto collagen-coated flexible membranes and grown to 70-80% confluence. Membranes were then deformed at 10 cycles per minute by the application of 135 mmHg subatmospheric pressure. This corresponded to strain levels of 0-24% from the centre to extremity of the flexible membrane. We show that a minimum of 15% cell stretch is required to significantly stimulate the fibroblast orientation response. focal adhesion kinase (FAK), p38 and Rho were activated in fibroblasts exposed to cyclic stretch and incubation of cells with anti-integrin beta1 before the application of stretch abrogated fibroblast orientation, as well as FAK, p38 and Rho activation. Fibroblast orientation in response to cyclic stretch is mediated at least in part by integrin beta1 through phosphorylation of FAK, p38 and activation of Rho.