Cellular Cruise Control: Energy dissipation regulates collective migration in epithelia

Collective cellular migration is crucial for several key biological processes such as wound healing, morphogenesis, and metastasis. The mechanisms that regulate this dynamic migratory behavior are a complicated consortium of intracellular cytoskeletal mechanics and signaling pathways, intercellular cell-cell adhesion, and extracellular interactions with the environment. Here, we develop a data-driven agent-based model that predicts collective migratory behavior from past energy dissipation alone, considering cell-substrate friction and viscous cell-cell interactions. Using this model, we are able to accurately predict tissue traction forces from phase microscopy data, removing the need for more invasive and complicated experimental methods such as TFM. Additionally, we show that cells self-regulate their migratory behavior and that the past energy expenditure of a cell is an accurate predictor of its future behavior. Finally, we perform canonical electrotaxis (the guided migration of cells experiencing an electrical current) experiments to show that exogenous migratory cues shift cell self-regulation to different modes of migration. Our model accurately recapitulates the phenomenon wherein epithelia exhibit a migratory slowdown when undergoing prolonged stimulation and has applications in developing closed-loop control of epithelial migration.

Funding: IBB: NSF GRFP, DJC: NSF CAREER, RB: UKRI