Tensegrity: the interplay between the tensile forces generated by the cytoskeleton and membrane tension

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One of the most fascinating and important properties of living systems is their ability to cope with physical damage. This property is manifested in both single cells and multicellular systems and is broadly conserved not only in a number of different animal phyla, but in plants as well. Because of it obvious clinical importance, multicellular wound healing has long been the subject of intense scrutiny. Repair of plasma membrane wounds in single cells, in contrast, has been overlooked until recently. At least two mechanisms have been described: an extremely rapid membrane fusion event that provides an immediate block to the inrush of ions that would otherwise kill the cell, and a slower contractile response in which a transient circumferential ring of actin and myosin assembles around the wound and closes. The primary goal of the proposed research program is to characterize the mechanisms that regulate assembly and closure of transient contractile arrays - specifically, this research program is designed to examine cellular tensegrity at the cellular and molecular level. More precisely, we aim to identify and describe how changes in tension at the plasmalemma, both intracellularly and extracellularly affect the signaling events that regulate formation of contractile events of the cytoskeleton aimed at restoring tensegrity after an injury or necessary for canonical mammalian cell division. Xenopus oocytes and mammalian cultured cells will be used as a model systems, and a combination of biophysical, microscopic, and recombinant DNA-based approaches will be employed to test the relationships between cell tension, local increases in the upstream regulators of the cytoskeleton, and intracellular calcium, in the recruitment and assembly of transient contractile arrays. While single cell wound repair is an important process in its own right, the fundamental assumptions that underlie this project is that the importance of the contractile ring wound response extends well beyond the single cell.