Learning the dynamics of cell–cell interactions in confined cell migration

Significance When cells migrate collectively, such as to heal wounds or invade tissue, they coordinate through cell–cell interactions. While much is known about the molecular basis of these interactions, the system-level stochastic dynamics of interacting cell behavior remain poorly understood. Here, we design an experimental “cell collider,” providing a large ensemble of interacting cell trajectories. Based on these trajectories, we infer an interacting equation of motion, which accurately predicts characteristic pairwise collision behaviors of different cell lines, including reversal, following, or sliding events. This data-driven approach can be used to quantitatively study how molecular perturbations control cell–cell interactions and may be extended to larger cell collectives, where the inferred interactions could provide key insights into multicellular dynamics. The migratory dynamics of cells in physiological processes, ranging from wound healing to cancer metastasis, rely on contact-mediated cell–cell interactions. These interactions play a key role in shaping the stochastic trajectories of migrating cells. While data-driven physical formalisms for the stochastic migration dynamics of single cells have been developed, such a framework for the behavioral dynamics of interacting cells still remains elusive. Here, we monitor stochastic cell trajectories in a minimal experimental cell collider: a dumbbell-shaped micropattern on which pairs of cells perform repeated cellular collisions. We observe different characteristic behaviors, including cells reversing, following, and sliding past each other upon collision. Capitalizing on this large experimental dataset of coupled cell trajectories, we infer an interacting stochastic equation of motion that accurately predicts the observed interaction behaviors. Our approach reveals that interacting noncancerous MCF10A cells can be described by repulsion and friction interactions. In contrast, cancerous MDA-MB-231 cells exhibit attraction and antifriction interactions, promoting the predominant relative sliding behavior observed for these cells. Based on these experimentally inferred interactions, we show how this framework may generalize to provide a unifying theoretical description of the diverse cellular interaction behaviors of distinct cell types.