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Cells crawling through tissues migrate inside a complex fibrous environmentcalled the extracellular matrix (ECM), which provides signals regulatingmotility. Here we investigate one such well-known pathway, involving mutuallyantagonistic signalling molecules (small GTPases Rac and Rho) that control theprotrusion and contraction of the cell edges (lamellipodia). Invasive melanomacells were observed migrating on surfaces with topography (array of posts),coated with adhesive molecules (fibronectin, FN) by Park et al., 2016. Severaldistinct qualitative behaviors they observed included persistent polarity,oscillation between the cell front and back, and random dynamics. To gaininsight into the link between intracellular and ECM signaling, we comparedexperimental observations to a sequence of mathematical models encodingdistinct hypotheses. The successful model required several critical factors.(1) Competition of lamellipodia for limited pools of GTPases. (2) Protrusion /contraction of lamellipodia influence ECM signaling. (3) ECM-mediatedactivation of Rho. A model combining these elements explains all three cellularbehaviors and correctly predicts the results of experimental perturbations.This study yields new insight into how the dynamic interactions betweenintracellular signaling and the cell's environment influence cell behavior.

A mathematical model coupling polarity signaling to cell adhesion explains diverse cell migration patterns