Collective directional memory controls the range of epithelial cell migration

Cell migration is a fundamental behavior in multicellular development, regeneration, and homeostasis, which is deregulated in cancer. Epithelial cells migrate individually when isolated and collectively within a tissue. However, how interactions between cells affect their ability to explore space and their sensitivity to guidance signals is poorly understood. We show that isolated cells that are persistent random walkers adopt a super-diffusive behavior in an epithelium. The effect is stronger than external guidance cues and enables cells to reach greater distances than when isolated. This behavior is consistent with a fractional Brownian motion that emerges from velocity coordination between neighboring cells with intact intercellular adhesion. Furthermore, we show how the molecular stability and mechanosensitivity of adhesion complexes, both linked to the ability of the adhesion protein vinculin to dimerize, ultimately regulate the speed of collective migration and the sensitivity to guidance signals. Together, our results show how cell speed, persistence, and directionality define the efficiency of spatial cell exploration on short, intermediate, and long time scales, respectively.