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BP: Fachverband Biologische Physik

BP 39: Optogenetics for the Cytoskeleton - Focus Session organized by Ulrich Schwarz

BP 39.2: Vortrag

Mittwoch, 22. März 2017, 10:00–10:15, SCH A251

Collective dynamics determine selection and regulation of leaders during epithelial wound healing — •Medhavi Vishwakarma, Tamal Das, and Joachim P. Spatz — Department New Materials and Biosciences, Max-Planck-Institute for Intelligent Systems, Stuttgart

Collective migration involves coordinated movement of several cells, and influences many biological processes including embryogenesis, wound healing, and cancer metastasis. The prevalent view on collective cell migration, especially in the context of epithelial cells during wound healing, assumes a hierarchical leader-follower organization and belittles the contribution of follower cells in choosing or regulating the leaders. Here, we report and analyse distinct phases of collective migration during wound closure and demonstrate how collective dynamics influence selection and regulation of leader cells in these phases. We found that in the preparatory phase, before the initiation of migration (Phase 0), the selection of leader cells at the epithelial wound margin is largely governed by dynamic heterogeneity of the followers in the monolayer. Long before the prospective leaders actually start displaying their phenotypic peculiarities, cells behind them manifest stochastic augmentations in the traction forces and monolayer stresses, and display large perimeter-to-area ratio indicating a local unjamming. Strikingly, the length scale of this collective dynamics matches with the distance between two emerging leaders. Furthermore, It is also possible to control the leader cell formation by introducing followers with high contractile forces at the back. For that, we used an optogenic technique involving a photo-excitable form of RhoA to transiently increase the RhoA activation and hence the cellular traction stresses. Upon photoactivation of RhoA in the followers, we could spatially bias the formation of leaders at the interface. As the migration progresses from the phase 1 to the phase 2, the number of followers per leader is limited by formation of new leaders at the margin and this limit is again set by the length scale of cell-cell force transmission. Any perturbations in mechanical forces that modifies the force correlation lengths and hence the collective dynamics of the system, invariably enforces a change in the number of followers per leader thereby modifying the time required to transit from one phase to the other. Together, these findings provide a novel insight into formation and regulation of leader cells, and indicate integrative leader-follower interactions during wound closure.