Emergence of bidirectional cell laning from collective contact guidance

Directed collective cell migration is central to morphogenesis, wound healing and cancer progression. Although the molecular anisotropy of the microenvironment guides this migration, its impact on cell flow patterns remains unexplored. Here we show that subcellular microgrooves elicit a polar mode of collective migration in bidirectional lanes, whose widths reach hundreds of micrometres. This directed form of flocking is observed in vitro with a confluent monolayer of human bronchial epithelial cells whose dynamics is chaotic on featureless substrates. A hydrodynamic theory of active polar fluids and corresponding numerical simulations account for this disorder-to-laning transition and further predict that anisotropic friction associated with the grooves lowers the transition threshold, which we confirm experimentally. Therefore, the microscopic anisotropy of the environment both directs collective cell motion along the substrate easy axis and shapes cell migration patterns. The flow patterns induced by this collective contact guidance are different from those resulting from supracellular confinement, demonstrating that collective migration is impacted by the different length scales of the microenvironment. Our findings offer a strategy for directing cells to specific geometries and functions in tissue engineering applications such as organoid morphogenesis. Supracellular cues play a key role in directing collective cell migration in processes such as wound healing and cancer invasion. New findings emphasize the importance of all length scales of the microenvironment in shaping cell migration patterns.