Computational Modeling of the Dynamics of Spatiotemporal Rho GTPase Signaling: A Systematic Review

The Rho family of GTPases are known to play pivotal roles in the regulation of fundamental cellular processes, ranging from cell migration and polarity to wound healing and regulation of actin cytoskeleton. Over the past decades, accumulating experimental work has increasingly mapped out the mechanistic details and interactions between members of the family and their regulators, establishing detailed interaction circuits within the Rho GTPase signaling network. These circuits have served as a vital foundation based on which a multitude of mathematical models have been developed to explain experimental data, gain deeper insights into the biological phenomenon they describe, as well as make new testable predictions and hypotheses. Due to the diverse nature and purpose of these models, they often vary greatly in size, scope, complexity, and formulation. Here, we provide a systematic, categorical, and comprehensive account of the recent modeling studies of Rho family GTPases, with an aim to offer a broad perspective of the field. The modeling limitations and possible future research directions are also discussed.