The spontaneous emergence of patterns in cell collectives is a multidisciplinary field that lies at the intersection of nonequilibrium physics and cellular biology, which sheds light on intricate biological phenomena. Despite considerable efforts, the precise integration of mechanical and chemical signaling, which drive these collective behaviors, remains elusive at the cellular level. In this study, we highlight the conserved occurrence of spatiotemporal waves involving both cell density and extracellular signal-regulated kinase (ERK) activation, observed in vitro and in vivo. We demonstrate that intercellular coupling, mediated by ERK-driven mechanochemical feedback, enables guidance cues to traverse over long distances. We further show that the patterns can be quantitatively explained by the coupling between active cellular tensions and the mechanosensitive ERK pathway—supported by our proposed mathematical model and with the backing of mechanical and optogenetic perturbation experiments. This study establishes a crucial link between the biophysical origins of spatiotemporal instabilities and the fundamental design principles that govern the efficient long-range transference of biological information.
