Competing forces of polarization and adhesion modulate directional migration bias in a minimal model.

Left-right axis specification establishes embryonic laterality through asymmetric signaling cascades originating at the cellular scale. A recent experiment reports the presence of a directionality bias in confined pairs of endothelial (and fibroblast) cells exhibiting persistent circular motion, with cytoskeletal contractility modulating the direction. The relative simplicity of the experimental setup makes it a perfect testing ground for the physical forces that could endow this system with a tunable directional migration bias. We model self-propelling biological cells migrating in response to confinement, polarity, and pairwise repulsive forces. Our framework reproduces three key experimental observations: spontaneous persistent circular movement of confined cell pairs, emergence of directional bias when cells have nonidentical properties, and parameter-modulated switching of the rotation direction. Two key assumptions are required: an internal torque arising from cytoskeletal organization (previously observed in other cellular systems) and nonidentical polarity response between cells, which introduces a difference in how quickly each cell reorients its migration direction. New experiments on daughter cell pairs support this influence of differences in cellular properties. Tuning the polarity response timescale (or strength) relative to centering forces from confinement and cell-cell adhesion can amplify or reverse the directional migration bias. A fast-slow analysis of the doublet dynamics reveals a geometric mechanism underlying the directional reversal: when cells are mechanically linked into a rigid pair, polarity is pinned radially inward by confinement; a one-sided (clockwise) deflection of this inward polarity generates orbital motion in the opposite (counterclockwise) direction.