Contact-induced differential persistence as a mechanism for cell sorting

Cell sorting corresponds to the spatial organisation of cells by type or function, which is central to tissue morphogenesis and arises from the interplay of mechanical, biochemical, and cellular processes. While variations in cell motility are known to influence sorting, the mechanisms by which cell-cell interactions drive symmetric or asymmetric segregation remain poorly understood. Using co-cultures of genetically modified HEK293 cells, we uncover a sorting mechanism based on heterotypic contact-induced differential persistence. This causes a temporary increase in the persistence of motion of a cell of one type after interacting with a cell of another type. Through theoretical modelling and numerical simulations, we demonstrate that this mechanism alone can drive sorting and break the symmetry of the segregation dynamics, and that the degree of sorting is maximized for an optimal duration of the enhanced persistence state. Furthermore, we show that differential persistence can work in synergy with other motility-based mechanisms to enhance sorting, even under crowded conditions. These results show that persistence, independent of self-propulsion speed, can drive segregation, providing a minimal physical framework for sorting in cellular systems and active matter. How mixed cell populations segregate into distinct groups is a key question in development and tissue organization. Combining experiments and simulations, the authors show that brief contact between different cell types increases directional persistence and can drive efficient cell sorting.