Geometry adaptation of protrusion and polarity dynamics in confined cell migration

Cell migration in confining physiological environments relies on the concerted dynamics of several cellular components, including protrusions, adhesions with the environment, and the cell nucleus. However, it remains poorly understood how the dynamic interplay of these components and the cell polarity determine the emergent migration behavior at the cellular scale. Here, we employ a data-driven theoretical approach to develop a mechanistic model for confined cell migration, revealing how the cellular dynamics adapt to confining geometries. Specifically, we use experimental data of joint protrusion-nucleus migration trajectories of cells on confining micropatterns to systematically determine a model linking the stochastic dynamics of cell polarity, protrusions, and nucleus. Our model indicates that the cellular dynamics adapt to confining constrictions through a switch in the polarity dynamics from a negative to a positive, self-reinforcing feedback loop. This feedback loop leads to stereotypical cycles of protrusion-nucleus dynamics that drive the migration of the cell through constrictions. Our data-driven theoretical approach therefore identifies polarity feedback adaptation as a key mechanism in confined cell migration.