Data-Driven Theory Reveals Protrusion and Polarity Interactions Governing Collision Behavior of Distinct Motile Cells

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. Remarkably, 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 behaviors of motile cells.