Publication date: 25th July 2016
Collective cell migration is ubiquitous among biological entities. The prevalent view of collective cell migration assumes a hierarchical leader-follower organization and belittles the contribution of follower cells in choosing or regulating the leaders. Furthermore, the biophysical link between formation and regulation of leader cells remains missing. Here, we uniquely report and analyse three distinct phases of collective cell migration and demonstrate how cellular-level shared decision-making process influence formation and regulation of leader cells in these phases. Investigating preparatory phase before the migration (Phase 0), we show that the selection of leader cells in the epithelial wound margin ultimately depends on the pre-migratory dynamics of the inner follower cells situated immediately behind the future leaders. This inherent dynamics override any preliminary bias imparted directly to the leading edge. Immediately after the initiation of migration (Phase 1), leaders show their phenotype and drive the movement. In this phase, pluricellular actin belt at the margin tightly regulate the propensity of leader cells. Non-leader marginal cells here reorient their focal adhesions towards the leaders thereby following the latter. Later during the migration (Phase 2), new leaders emerged from already existing outgrowths in order to minimize the tension at curvature-interface when the size of outgrowths increased. In the end, we show that in all phases, pharmacological perturbation in mechanical forces that modifies the force correlation lengths, invariably enforces a change in the length scale of guidance and therefore, the propensity of leader cells at the wound margin. Together, these findings provide a novel system-insight into formation and regulation of leader cells during collective cell migration.
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