Collective Cell Radial Ordered Migration in Spatial Confinement

Abstract Collective cells, a typical active matter system, exhibit complex coordinated behaviors fundamental for various developmental and physiological processes. The present work discovers a collective radial ordered migration behavior of NIH3T3 fibroblasts that depends on persistent top‐down regulation with 2D spatial confinement. Remarkably, individual cells move in a weak‐oriented, diffusive‐like rather than strong‐oriented ballistic manner. Despite this, the collective movement is spatiotemporal heterogeneous and radial ordering at supracellular scale, manifesting as a radial ordered wavefront originated from the boundary and propagated toward the center of pattern. Combining bottom‐up cell‐to‐extracellular matrix (ECM) interaction strategy, numerical simulations based on a developed mechanical model well reproduce and explain above observations. The model further predicts the independence of geometric features on this ordering behavior, which is validated by experiments. These results together indicate such radial ordered collective migration is ascribed to the couple of top‐down regulation with spatial restriction and bottom‐up cellular endogenous nature.