Collective directional memory controls the range of epithelial cell migration

Cell migration is a fundamental behavior involved 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. Here, we show that isolated cells that are persistent random walkers adopt a superdiffusive behavior in an epithelium. The effect is stronger than external guidance cues and enables cells to reach greater distances than when isolated. This directional memory emerges from fractional Brownian motion that relies on velocity coordination between neighboring cells with intact cytoskeletal connections to intercellular adhesion complexes. Furthermore, we show how the stability and mechanosensitivity of adhesion complexes ultimately regulate the speed of collective migration and the sensitivity to guidance signals via dimerization of the adhesion protein vinculin. 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.