Velocity alignment leads to high persistence in confined cells.

Many cell types display random motility on two-dimensional substrates but crawl persistently in a single direction when confined in a microchannel or on an adhesive micropattern. Does this imply that the motility mechanism of confined cells is fundamentally different from that of unconfined cells? We argue that both free- and confined-cell migration may be described by a generic model of cells as "velocity-aligning" active Brownian particles previously proposed to solve a completely separate problem in collective cell migration. Our model can be mapped to a diffusive escape over a barrier and analytically solved to determine the cell's orientation distribution and repolarization rate. In quasi-one-dimensional confinement, velocity-aligning cells maintain their direction for times that can be exponentially larger than their persistence time in the absence of confinement. Our results suggest an important connection between single- and collective-cell migration: high persistence in confined cells corresponds with fast alignment of velocity to cell-cell forces.