Optogenetic control of collective dynamics in Epithelial Cells

Obiettivo

Collective cell motility states, such as multicellular flocking and jamming, are active matter states that play important roles in development and disease. However, much of the dynamics of these collective states remains to be discovered. The goal of this proposal 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 and contraction on-demand. By combining optogenetics with traction force microscopy, we will first study how single epithelial cells reshape their traction forces in response to activation of RhoA, Rac1 and CDC42. We will then investigate collective coordination of intrinsic forces and movements in response to different patterns of photoactivation of these RhoGTPases. Specifically, we will induce and steer flocks made of several cells, and we will jam/unjam well-defined regions in monolayers near the jamming transition. Active gel models will help us identify characteristic mechanical profiles of single- and multi-cellular motility. The project will yield new approaches to understand and control epithelial dynamics at the mesoscale, opening new avenues at the intersection of active matter physics and biology.