Competing forces of polarization and confinement generate cellular chirality in a minimal model (2510.11642v1)

Abstract: Left-right axis specification is a vital part of embryonic development that establishes the left and the right sides of an embryo. Asymmetric organ morphogenesis follows asymmetric signaling cascades, which in turn follow asymmetric events on the cellular scale. In a recent study, Badih et al.\ reported cell-scale movement asymmetries in spontaneously rotating pairs of endothelial cells confined to a circular fibronectin-coated island. Importantly, the authors demonstrate that cytoskeletal contractility modulates the chirality bias. The relative simplicity of the experimental setup make it a perfect testing ground for the physical forces that could endow this system with rotational movement and biases, but these forces have yet to be stated. We model self-propelling biological cells migrating in response to confinement, polarity, and pairwise repulsive forces. For the first time, we are able to reproduce not only the coherent angular movement of a confined pair of cells biased in a direction but also a contractility-modulated chirality bias. To arrive at these modeling results, two key assumptions are needed: an intrinsic orientation bias (previously observed in other cellular systems), and a difference between the cells in their velocity alignment response, which endows the system with a difference in the timescales of dynamics. Tuning the timescale (or strength) of polarity response relative to the remaining forces (confinement and cell-cell interaction), can amplify or reverse the CW bias. We present a coherent theory, based on dynamical system analysis, that captures chirality emergence in a singlet and doublet cell system.