  Directed collective cell migration is central in morphogenesis, wound healing
and cancer progression1,2. Although it is well-accepted that the molecular
anisotropy of the micro-environment guides this migration3,4, its impact on the
pattern of the cell flows remains largely unexplored. Studying confluent human
bronchial epithelial cells (HBECs) in vitro, we show that subcellular
microgrooves elicit a polar mode of collective migration in millimeter-long
bidirectional lanes that are much wider than a cell size, even though cell
flows are highly disordered on featureless surfaces 5. This directed
flocking-like transition6,7 can be accounted for by a hydrodynamic theory of
active polar fluids and corresponding numerical simulations. This model further
predicts that anisotropic friction resulting from the grooves lowers the
threshold of the transition, which we confirm experimentally. Therefore,
microscopic anisotropy of the environment not only directs the collective
motion of the cells in the easy direction, but also shapes the cell migration
pattern. Flow patterns induced by collective contact guidance are thus markedly
different from those induced by supracellular confinement8, demonstrating that
all length-scales of the micro-environment must be considered in a
comprehensive description of collective migration. Furthermore, artificial
microtopographies designed from theoretical considerations can provide a
rational strategy to direct cells to specific geometries and functions, which
has broad implications, for instance, for tissue engineering strategies in
organoid morphogenesis.
