Objective   To assess the effects of cyclic stretch on fibroblast orientation in order to find the appropriate cyclic stretch to cause maximum fibroblast orientation and to explore the mechanism of cell signalling since cells are known to orient in response to the application of mechanical forces.    Methods   Human forehead dermal fibroblasts were seeded onto collagen coated flexible membranes. Membranes were then deformed at 10 cycles per minute by the application of 135 mmHg subatmospheric pressure. This corresponded to strain levels of 0% to 24% from the center to extremity of the flexible membrane. Cells orientation angles w

ere studied by inverted microscopy. Integrin β

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distribution were studied with  immunocytochemical staining and confocal microscopy. Integrin β

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expression and focal adhesion kinase (FAK) phosphorylation were analyzed with Western blot analysis.    Results   A minimum of 15% cell stretch was required to significantly stimulate the fibroblast orientation response. Cyclic stretch induced integrin β

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redistribution and FAK phosphorylation. Incubation of cells with anti-integrin β

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prior to the application of stretch abrogated fibroblast orientation and FAK phosphory-lation.    Conclusion   Fibroblast orientation in response to cyclic stretch is mediated at least in part by integrin β

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through phosphorylation of FAK.