Cellular crowd control: improving external control of collective cell migration by modulating existing cell-cell coordination*

While there is increasing interest in approaches to reprogram collective cellular migration, a process critical for multicellular processes such as regeneration and development, little is known about what happens when external 'commands' conflict against natural collective behaviors of the collective system. In this study, we investigate two major questions: 1) how much does the strength of an endogenous collective behavior in a tissue limit our ability to control its collective cell migration, and 2) how can we circumvent such limitations? Using a bioelectric stimulus—electrotaxis—to externally program cell migration in large, cultured layers of primary mouse skin monolayers, we study how strong endogenous cell coordination created through strong cell-cell coupling via cadherin adhesion can compete with external migration commands, as well as methods that can be used to optimize external control of cellular collectives. We hope this study will pave the way for future approaches to better analyze, control, and synergize with existing collective behaviors.