OptoEpiC · Optogenetic control of collective dynamics in Epithelial Cells

Optogenetic control of collective dynamics in Epithelial Cells

Collective cell motility states, such as multicellular flocking and jamming, play important roles in development and disease. However, much of the physical force dynamics of these collective states remains to be discovered. A key advance in understanding the dynamics of collective systems would be to control collective cellular propulsion spatially and temporally. This, however, is presently impossible and current studies are therefore limited to infer the behavior of the system from observations of key variables rather than from their control. The goal of this project is to use optogenetics to control and understand collective cell dynamics. Optogenetics allows to control cell mechanics with unprecedented temporal and spatial precision by photoactivating the molecular machinery that regulates cell protrusion, contraction and migration, on-demand. We combine the precise control of optogenetics with traction force microscopy, which allows to study the physical forces of cells and cell clusters. This combination allows us to study collective cell dynamics in ways that were impossible before. We first studied how single epithelial cells react to optogenetic “photoactivation” of the Rho-GTPases RhoA, Rac1 and CDC42. We then investigated the collective coordination and movements in response to different patterns of photoactivation of these Rho-GTPases. Specifically, we optogenetically guided and steered flocks/clusters made of several cells, and we used optogenetic control to set cell monolayers into motion, which had not been achieved before. This project yields new approaches to understand and control epithelial cell dynamics at the mesoscale, opening new avenues at the intersection of active matter physics and biology.

Data: CORDIS, © European Union