Feedback onto cellular polarization from paxillin, implications for migrating cells

Speaker: Laurent MacKay

Date: Wed, Apr 14, 2021

Location: Zoom, Online, PIMS, University of British Columbia

Conference: Mathematical Biology Seminar

Subject: Mathematics, Mathematical Biology

Class: Scientific


Cellular polarization plays a critical during cellular differentiation, development, and cellular migration through the establishment of a long-lived cell-front and cell-rear. Although mechanisms of polarization vary across cells types, some common biochemical players have emerged, namely the RhoGTPases Rac and Rho. The low diffusion coefficient of the active form of these molecules combined with their mutual inhibitory interaction dynamics have led to a prototypical pattern-formation system that can polarizes cell through a non-Turing pattern formation mechanism termed wave-pinning. We investigate the effects of paxillin, a master regulator of adhesion dynamics, on the Rac-Rho system through a positive feedback loop that amplifies Rac activation. We find that paxillin feedback onto the Rac-Rho system produces cells that (i) self-polarize in the absence of any input signal (i.e., paxllin feedback causes a Turing instability) and (ii) become arrested due to the development of multiple protrusive regions. The former effect is a positive finding that can be related to certain cell-types, while the latter outcome is likely an artefact of the model. In order to minimize the effects of this artefact and produce cells that can both self-polarize as well as migrate for extended periods of time, we revisit some of model's parameter values and use lessons from previous models of polarization. This approach allows us to draw conclusions about the biophysical properties and spatiotemporal dynamics of molecular systems required for autonomous decision making during cellular migration.