Regulation of Focal Adhesion Initiation by Lipids and Membrane Bending

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The research objective of this award is to understand the very early parts of how cells adhere to surfaces such as natural extracellular matrices and artificial surfaces used in biomaterials. Specifically, this research will investigate how the membrane controls the transport of lipids and the recruitment of important adhesion molecules to adhesion plaques. These experiments will use advanced microscopes capable of measuring dynamics of cellular adhesions and molecular dynamics in these structures. If successful, these measurements would lead to a better understanding of cellular adhesion dynamics and why atherosclerotic lesions form in areas of low and oscillating fluid shear stress such as at blood vessel bifurcations and near stents. It may also be important for shear-induced vasodilation, which is known to counteract pressure-induced myogenic constriction in small arteries and thus is an important component of blood pressure control and hypertension. If successful, these studies would add significantly to the field's understanding of mechanosensing in particular and molecular scale functional organization of plasma membranes in general. This understanding may assist in future testing of mechanosensation theories and in the development of new biomechanical mimetics, such as unilamellar vesicles with proteins, proteoglycans, and cytoskeleton. Since almost all cells need to sense and apply force, these studies may have broad implications for many mechanobiological processes including bone remodeling, stem cell differentiation, and developmental biology. The proposed research on membrane mechanobiology will be integrated into graduate training and in undergraduate honors thesis preparation. This training will form the basis of outreach to young scientists (grades 6-12) in which molecular scale mechanobiology is made more accessible through modern 3-D visualization. Such outreach will provide opportunities to reach underrepresented groups such as women and minorities and students in rural Pennsylvania, who visit Penn State frequently as they consider their higher education options.