This talk focuses on recent investigations of the mechanical properties of intercellular junctions and the transduction of mechanical cues across cell-cell junctions to the cytoskeletons of adjacent cells. This work is motivated by ventilator induced lung injury where mechanical pressure triggers biochemical changes in the pulmonary endothelium that compromise tissue barrier properties. We use mechanical probes and live cell imaging to identify rapid, early signalling cascades triggered by the mechanical stimulation of cadherin adhesions. Studies tested an initial postulate that alpha catenin, at cadherin junctions, is the primary force transducer at cadherin-based cell-cell junctions. We directly tested this model, and identified rudiments of the mechanotransduction mechanism, as well as key proteins essential for this function. More recent studies further revealed that cadherin-based mechanotransduction, not only actuates local cytoskeletal remodelling, but also triggers global signals that perturb integrins, globally alter cell mechanics, and disturb cell-cell junctions far from the location of the initial perturbation. The latter changes are due to a second mechanotransduction pathway that involves signalling cascades, in addition to local actin remodeling, and reveals that cadherins, integrins, and the actomyosin cytoskeleton form an integrated mechanically sensitive network that globally regulates tissue integrity.
I received my Ph.D. in Biophysical Chemistry from Cornell University in 1988. My broad research interests focus on the biophysics of cell adhesion and mechanotransduction, and the role of adhesion and cell mechanics in human disease, tissue morphogenesis, and tissue homeostasis. My lab has substantial expertise and capabilities in force measurements of protein and cell mechanics, dynamic imaging of intracellular cascades triggered by cadherin-based mechanotransduction, and different methods of mechanically perturbing cells. We use a combination of mechanical probes, live cell and high-resolution imaging, and biochemical methods.