Viscoelastic relaxation of collagen networks provides a self-generated directional cue during collective migration

There is growing evidence that the physical properties of the cellular environment can impact cell migration. However, it is not currently understood how active physical remodeling of the network by cells affects their migration dynamics. Here, we study collective migration of small clusters of cells on deformable collagen-1 networks. Combining theory and experiments, we find that cell clusters, despite displaying no apparent internal polarity, migrate persistently and generate asymmetric collagen gradients during migration. We find that persistent migration can arise from viscoelastic relaxation of collagen networks, and reducing the viscoelastic relaxation time by chemical crosslinking leads to a reduction in migration persistence. Single cells produce only short range network deformations that relax on shorter timescales, which leads to lower migration persistence. This physical model provides a mechanism for self-generated directional migration on viscoelastic substrates in the absence of internal biochemical cues.