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Collective cell migration offers a rich field of study for non-equilibrium physics and cellular biology, revealing phenomena such as glassy dynamics [1], pattern formation [2] and active turbulence [3]. However, how mechanical and chemical signaling are integrated at the cellular level to give rise to such collective behaviors remains unclear. We address this by focusing on the highly conserved phenomenon of spatio-temporal waves of density [2,[4][5][6][7][8] and ERK/MAPK activation [9][10][11], which appear both in vitro and in vivo during collective cell migration and wound healing. First, we propose a biophysical theory, backed by mechanical and optogenetic perturbation experiments, showing that patterns can be quantitatively explained by a mechano-chemical coupling between three-dimensional active cellular tensions and the mechano-sensitive ERK/MAPK pathway. Next, we demonstrate how this biophysical mechanism can robustly induce migration in a desired orientation, and we determine a theoretically optimal pattern for inducing efficient collective migration fitting well with experimentally observed dynamics. We thereby provide a bridge between the biophysical origin of spatio-temporal instabilities and the design principles of robust and efficient long-ranged migration. ⇤ Equal contribution †

No abstract

Living tissues are characterized by an intrinsically mechanochemical interplay of active physical forces and complex biochemical signalling pathways. Either feature alone can give rise to complex emergent phenomena, for example mechanically driven glassy dynamics and rigidity transitions, or chemically driven reaction-diffusion instabilities. An important question is how to quantitatively assess the contribution of these different cues to the large-scale dynamics of biological mate- rials. We address this in MDCK monolayers, considering both mechanochemical feedbacks between ERK signalling activity and cellular density as well as a mechanically active tissue rheology via a self-propelled vertex model. We show that the relative strength of active migration forces to mechanochemical couplings controls a transition from uniform active glass to periodic spatiotemporal waves. We parameterize the model from published experimental datasets on MDCK monolayers, and use it to make new predictions on the correlation functions of cellular dynamics and the dynamics of topological defects associated with the oscillatory phase of cells. Interestingly, MDCK monolayers are best described by an intermediary parameter region in which both mechanochemical couplings and noisy active propulsion have a strong influence on the dynamics. Finally, we study how tissue rheology and ERK waves feedback on one another, and uncover a mechanism via which tissue fluidity can be controlled by mechanochemical waves both at the local and global levels.