Collective cell migration offers a rich field of study for non-equilibrium physics and cellular biology, revealing phenomena such as glassy dynamics, pattern formation and active turbulence. However, how mechanical and chemical signalling are integrated at the cellular level to give rise to such collective behaviours remains unclear. We address this by focusing on the highly conserved phenomenon of spatiotemporal waves of density and extracellular signal-regulated kinase (ERK) activation, 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 mechanochemical coupling between active cellular tensions and the mechanosensitive ERK pathway. Next, we demonstrate how this biophysical mechanism can robustly induce long-ranged order and migration in a desired orientation, and we determine the theoretically optimal wavelength and period for inducing maximal migration towards free edges, which fits well with experimentally observed dynamics. We thereby provide a bridge between the biophysical origin of spatiotemporal instabilities and the design principles of robust and efficient long-ranged migration.

集体细胞迁移为非平衡物理学和细胞生物学提供了广阔的研究领域，揭示了诸如玻璃动力学，模式形成和活跃湍流等现象。但是，尚不清楚如何在细胞水平上整合机械和化学信号传导以引起这种集体行为。我们通过集中于高度保守的时空波密度和细胞外信号调节激酶（ERK）激活现象来解决此问题，这些现象在集体细胞迁移和伤口愈合过程中在体内和体外均会出现。首先，我们提出了一种生物物理理论，以机械和光遗传学扰动实验为后盾，表明可以通过活性细胞张力与机械敏感性ERK途径之间的机械化学耦合来定量解释模式。下一个，我们展示了这种生物物理机制如何在所需方向上稳健地诱导远距离有序运动和迁移，并且确定了诱导向自由边缘的最大迁移的理论上最佳的波长和周期，这与实验观察到的动力学非常吻合。因此，我们提供了时空不稳定性的生物物理起源与稳健而有效的远程迁移的设计原理之间的桥梁。