  Cells crawling through tissues migrate inside a complex fibrous environment
called the extracellular matrix (ECM), which provides signals regulating
motility. Here we investigate one such well-known pathway, involving mutually
antagonistic signalling molecules (small GTPases Rac and Rho) that control the
protrusion and contraction of the cell edges (lamellipodia). Invasive melanoma
cells were observed migrating on surfaces with topography (array of posts),
coated with adhesive molecules (fibronectin, FN) by Park et al., 2016. Several
distinct qualitative behaviors they observed included persistent polarity,
oscillation between the cell front and back, and random dynamics. To gain
insight into the link between intracellular and ECM signaling, we compared
experimental observations to a sequence of mathematical models encoding
distinct 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-mediated
activation of Rho. A model combining these elements explains all three cellular
behaviors and correctly predicts the results of experimental perturbations.
This study yields new insight into how the dynamic interactions between
intracellular signaling and the cell's environment influence cell behavior.
