Seminar Series in Quantitative Life Sciences and Medicine

Understanding cellular polarity and adhesion dynamics involved in cell motility using spatiotemporal models

Anmar Khadra (McGill University)
Tuesday April 30, 12-1pm
Montreal Neurological Institute, deGrandpre Communications Centre

Abstract: Cellular movement plays important roles in many (patho)physiological processes, such as immune cell response, growth of neuronal axons and cancer. The regulation of this movement depends on the interaction of several key proteins implicated in the development of cellular polarity (consisting of a front and a back) and the formation of protein complexes called adhesions. Adhesions anchor the cell to its substrate, allowing it to migrate. In CHO cells, three classes of adhesion can be identified based on size and dynamic properties: nascent adhesions, focal complexes and focal adhesions. When cells extends forward at the front, nascent adhesions assemble and anchor the leading edge to the substrate, while focal adhesions at the back disassemble, allowing detachment, retraction and forward movement. The dynamics of these processes are controlled by a number of regulatory factors, occurring on both cell-wide and adhesion-level scales. The coordination of these regulatory factors is complex, but insights into their dynamics can be gained from the use of mathematical/biophysical modeling techniques which integrate many of these components together. In this talk, I will present our recently developed molecularly-explicit and mechanosensitive models of cell polarity and adhesion dynamics to explore how local regulation of key adhesion proteins (including paxillin, rho family of GTPases and integrin) produce cell-wide polarization and nascent adhesion assembly/disassembly. The dynamics associated with various parameter regimes will be presented and insights into the mechanisms regulating adhesion dynamics will be provided.