Geometry adaptation of protrusion and polarity dynamics in confined cell migration

TL;DR

This study develops a mechanistic model combining data-driven inference to understand how cellular protrusion and polarity dynamics adapt to confined geometries, revealing feedback mechanisms that drive cell migration through constrictions.

Contribution

The paper introduces a novel model linking stochastic polarity, protrusion, and nucleus dynamics, highlighting feedback loop switches that adapt cell migration to confinement.

Findings

Polarity feedback switches from negative to positive in confinement.

Stereotypical protrusion-nucleus cycles drive migration.

Perturbations disrupt feedback, impairing migration.

Abstract

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 combine data-driven inference with a mechanistic bottom-up approach to develop a model for protrusion and polarity dynamics in 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 mechanistic model linking the stochastic dynamics of cell polarity, protrusions, and nucleus. This 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. Our model further reveals how this feedback loop leads to stereotypical cycles of protrusion-nucleus dynamics that drive the migration of the cell through constrictions. These cycles are disrupted upon perturbation of cytoskeletal components, indicating that the positive feedback is controlled by cellular migration mechanisms. Our data-driven theoretical approach therefore identifies polarity feedback adaptation as a key mechanism in confined cell migration.