Principles that govern competition or co-existence in Rho-GTPase driven polarization.

Abstract

Rho-GTPases are master regulators of polarity establishment and cell morphology. Positive feedback enables concentration of Rho-GTPases into clusters at the cell cortex, from where they regulate the cytoskeleton. Different cell types reproducibly generate either one (e.g. the front of a migrating cell) or several clusters (e.g. the multiple dendrites of a neuron), but the mechanistic basis for unipolar or multipolar outcomes is unclear. The design principles of Rho-GTPase circuits are captured by two-component reaction-diffusion models based on conserved aspects of Rho-GTPase biochemistry. Some such models display rapid winner-takes-all competition between clusters, yielding a unipolar outcome. Other models allow prolonged co-existence of clusters. We investigate the behavior of a simple class of models and show that while the timescale of competition varies enormously depending on model parameters, a single factor explains a large majority of this variation. The dominant factor concerns the degree to which the maximal active GTPase concentration in a cluster approaches a "saturation point" determined by model parameters. We suggest that both saturation and the effect of saturation on competition reflect fundamental properties of the Rho-GTPase polarity machinery, regardless of the specific feedback mechanism, which predict whether the system will generate unipolar or multipolar outcomes.

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10.1371/journal.pcbi.1006095

Publication Info

Chiou, Jian-Geng, Samuel A Ramirez, Timothy C Elston, Thomas P Witelski, David G Schaeffer and Daniel J Lew (2018). Principles that govern competition or co-existence in Rho-GTPase driven polarization. PLoS computational biology, 14(4). 10.1371/journal.pcbi.1006095 Retrieved from https://hdl.handle.net/10161/16662.

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Witelski

Thomas P. Witelski

Professor in the Department of Mathematics

My primary area of expertise is the solution of nonlinear ordinary and partial differential equations for models of physical systems. Using asymptotics along with a mixture of other applied mathematical techniques in analysis and scientific computing I study a broad range of applications in engineering and applied science. Focuses of my work include problems in viscous fluid flow, dynamical systems, and industrial applications. Approaches for mathematical modelling to formulate reduced systems of mathematical equations corresponding to the physical problems is another significant component of my work.


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