(601x) Acquisition of a Contractile Cell Phenotype Due to Mechanical Stresses in the Extracellular Environment

The fundamental mechanisms that initiate and promote degeneration of fibroblastic tissues within a variety of diseases are largely unknown. Tissue degeneration processes are commonly associated with aging and sometimes regarded as irreversible. However, recent studies of cell and tissue microenvironments have demonstrated that specific mechanical stimuli can regulate the onset of a variety degenerative mechanisms. Tissue degeneration via the acquisition of a contractile cell phenotype is one of the main changes observed in valvular diseases. 2D and 3D in vitro culture systems of valvular cells were used to investigate cell phenotype change, proliferation as well as migration, in this study. In addition, proteome surveys were conducted to investigate expression of cell membrane receptors and phosphoproteins. Proteome analyses shed light into key signaling pathways that link cell surface force-sensing proteins and the downstream biochemical signals that culminate in cellular degenerative responses. Control of cellular degeneration was also verified with the use of pharmacological inhibitors. The results presented here impact our understanding of cellular switches between fibroblastic and myofibroblastic phenotypes. This knowledge can be applied in engineering of living tissues with tunable mechano-chemical properties.