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Cellular migration is a complex phenomenon that involves the integration of many intracellular processes, allowing for an autonomous response to motility cues found in the cellular environment. Cellular protrusion and contraction, crucial aspects of motility and migration, are typically assumed to be driven by the RhoGTPases Rac and Rho, respectively. Near sites of protrusion, integrin-based adhesions spontaneously assemble and serve as both biochemical signaling hubs that feedback onto the local balance of Rac and Rho activity levels (e.g., through phosphorylation of the adhesion-associated protein paxillin) as well as force transmission points that cells can use to displace their bulk. This bidirectional feedback between biochemical activities and cellular displacement/mechanics makes understanding how cellular processes interact collectively with external cues to produce motility a challenging task. To complement the existing experimental methods used to study this system, we use computational modeling approaches to explore some facets of cellular motility. That includes (1) investigating how front-to-rear polarity, as well as certain motility phenotypes, are produced by the spatio-temporal dynamics of RhoGTPases arising from of a combination of their intrinsic molecular properties and biochemical signaling; (2) developing a biophysical model that describes the nanoscale formation of integrin-based adhesions capable of explaining experimental variations in integrin density and predicting the mechanical conditions required for self-assembly of adhesions; and (3) focusing on a cellular-scale model of protrusion to show how local interactions between maturing adhesions and VASP, an anti-capping protein for actin filaments, produce a variety of spatio-temporal patterns of protrusion, and how mechanical feedback through adhesions modifies these patterns. These results are compared to experimental findings to give more insight than would be feasible to achieve solely through experiments.

This seminar will be given online via Zoom. Details in attached poster.
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