Analyzing the spatiotemporal regulation of intracellular force transduction in living cells

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The ability of cells to sense and respond to mechanical forces is central to developmental, physiological and pathological processes. However, we just begin to understand how mechanical information is translated by cells into a biochemical response, and the molecular mechanisms of mechanotransduction are largely elusive. One reason for our limited understanding of force transduction on the molecular level is the lack of suitable techniques to study intracellular force propagation under physiologically relevant situations. Therefore, we recently developed a microscopic method that allows visualization and measurement of mechanical tension across single proteins in live cells with pico-Newton sensitivity. We will use this new technique to measure mechanical tension across proteins that associate with integrins, a class of cell surface receptors which mediate the interaction of cells with the extracellular matrix. Our experiments will reveal fundamental insights into the molecular processes of integrindependent force transduction and, as a result, increase our understanding of the mechanical aspects of cell migration.