Mechanical signal transduction plays a crucial role in the physiology of a variety of cell types including cardiac myocytes, endothelial cells, and bone cells. This process, also known as mechanotransduction, involves the conversion of a biophysical force into a cellular/molecular response leading to both rapid changes in kinase-mediated gene expression,, as well as slower adaptive changes in cytoskeletal arrangement. The overall objective of this study is to investigate the intracellular signaling cascades that are activated in response to mechanical stimulation. The hypothesis is that mechanical signals induce Rho-mediated cytoskeletal contractility. The tension generated is transmitted to the integrins leading to their aggregation and recruitment of FAK. Thus the focal adhesion complexes is driven from the inside of the cell by cytoskeletal contractility.. Controlled mechanical forces will be applied to trabecular bone growing within an in vivo bone chamber. Western blot analyses, kinases assays, and confocal imaging will be utilized to investigate the temporal activation of signaling molecules and cytoskeletal changes occurring in response to mechanical stimulation. Demonstration of the hierarchy of signaling molecules recruited to focal adhesion complexes and or the cytoskeleton in response to mechanical forces will provide insight to several downstream biologic processes including cellular proliferation, differentiation and adaptation.
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