Event

Abstract: Collective cell migration underpins key physiological processes, ranging from embryonic development to wound healing and cancer metastasis. While notable progress has been made in elucidating the required mechanisms, such as contact inhibition of locomotion, contact following of locomotion, and supracellular organization, the classification of collective motility modes remains incomplete. In this study, we focus on the migration patterns of small cell groups, specifically cohesive pairs of cells. Experimental observations reveal two distinct motility modes in Dictyostelium discoideum tandem pairs: the individual contributor (IC) mode, where each cell generates its own traction force dipole, and the supracellular (S) mode, characterized by a single traction force dipole. Intriguingly, IC mode predominates in Dictyostelium pairs, but S mode prevails in MDCK doublets, highlighting an apparent discrepancy in emergent modes between cell types. To uncover the mechanisms driving these diverse motility modes, we developed a new two-dimensional biophysical model incorporating mechanochemical details such as intercellular interactions, membrane contractility, and cell-surface adhesions, along with a new quantification method. Our model was capable of recapitulating experimental observations; IC mode emerged naturally in amoeboid doublets when both cells exerted similar traction forces, while S mode dominated with “stronger” leaders, that essentially pull on trailers. In contrast, simulations of MDCK-like pairs show roughly equal distribution of motility modes, but tunable with variations in cell-cell interactions, underscoring cell-type-specific adaptations in migration strategies. Our findings reveal how cell mechanics, particularly cell-surface interactions and cell membrane properties, drive collective migration of small cell groups. Extending our model to longer cell trains, we demonstrate its applicability across scales, providing a foundation for exploring collective migratory behavior in other physiological and pathological contexts.