Geometry-driven migration efficiency of autonomous epithelial cell clusters

Abstract

The directed migration of epithelial cell collectives through coordinated movements plays a crucial role in various physiological processes and is increasingly understood at the level of large confluent monolayers. However, numerous processes rely on the migration of small groups of polarized epithelial clusters in complex environments, and their responses to external geometries remain poorly understood. To address this, we cultivate primary epithelial keratocyte tissues on adhesive microstripes to create autonomous epithelial clusters with well-defined geometries. We show that their migration efficiency is strongly influenced by the contact geometry and the orientation of cell–cell contacts with respect to the direction of migration. A combination of velocity and polarity alignment with contact regulation of locomotion in an active matter model captures quantitatively the experimental data. Furthermore, we predict that this combination of rules enables efficient navigation in complex geometries, which we confirm experimentally. Altogether, our findings provide a conceptual framework for extracting the interaction rules of active systems from their interaction with physical boundaries, as well as design principles for collective navigation in complex microenvironments.