Data-driven theory reveals protrusion and polarity interactions governing collision behavior of distinct motile cells

TL;DR

This study develops a data-driven phenomenological model revealing that polarity-polarity and polarity-protrusion interactions govern the collision behavior of various motile cell types, unifying diverse behaviors under a common framework.

Contribution

The paper introduces a phenomenological theory identifying polarity-polarity and polarity-protrusion coupling as key mechanisms in cell collision dynamics, validated across multiple cell types and perturbations.

Findings

A single model captures behaviors of different cell types.

Polarity-polarity coupling varies with cell type and perturbations.

The model explains diverse collective migration behaviors.

Abstract

The migration behavior of colliding cells is critically determined by transient contact-interactions. During these interactions, the motility machinery, including the front-rear polarization of the cell, dynamically responds to surface protein-mediated transmission of forces and biochemical signals between cells. While biomolecular details of such contact-interactions are increasingly well understood, it remains unclear what biophysical interaction mechanisms govern the cell-level dynamics of colliding cells and how these mechanisms vary across cell types. Here, we develop a phenomenological theory based on 14 candidate contact-interaction mechanisms coupling cell position, protrusion, and polarity. Using high-throughput micropattern experiments, we detect which of these phenomenological contact-interactions captures the interaction behaviors of cells. We find that various cell types - ranging from mesenchymal to epithelial cells - are accurately captured by a single model with only two interaction mechanisms: polarity-protrusion coupling and polarity-polarity coupling. The qualitatively different interaction behaviors of distinct cells, as well as cells subject to molecular perturbations of surface protein-mediated signaling, can all be quantitatively captured by varying the strength and sign of the polarity-polarity coupling mechanism. Altogether, our data-driven phenomenological theory of cell-cell interactions reveals polarity-polarity coupling as a versatile and general contact-interaction mechanism, which may underlie diverse collective migration behavior of motile cells.