![]() ![]() Therefore, externally directing collective cell migration should allow us to not only better understand these processes, but also to formally program and engineer them for applications in regenerative medicine and tissue engineering, where large scale cellular motion is necessary, such as in wound healing ( 4–9). IntroductionĬollective cell migration is essential for many multicellular organisms and underpins diverse processes, spanning organ development to cancer invasion ( 1–3). We find that cells within stimulated tissues respond based on where they are in the tissue, and that such global commands induce reprogramming of innate collective cell behaviors even long after the stimulus stops. We investigated this by stimulating epithelial tissues to migrate ‘rightward’ using a bioelectric stimulus, electrotaxis, and mapped how different parts of the tissue responded to the same command, both during and after stimulation. A key challenge is to understand how a group responds to given migration ‘commands’ as a collective unit, particularly as such cues are often transient. Overall, this work demonstrates how externally driving the collective migration of a tissue can reprogram baseline cell–cell interactions and collective dynamics, even well beyond the end of the global migratory cue, and emphasizes the importance of considering the supracellular context of tissues and other collectives when attempting to program crowd behaviors.Ĭoordinated cell migration is critical in processes spanning development, healing, and disease accordingly, improving our ability to program and engineer such collective migration is an important goal. These unique dynamics suggested that programmed migration resets tissue mechanical state, which was confirmed by transient chemical disruption of cell–cell junctions, analysis of strain wave propagation patterns, and quantification of cellular crowd dynamics. Furthermore, at no point poststimulation did tissues return to their prestimulation behavior, instead equilibrating to a 3rd, new migratory state. ![]() Tissues clearly developed distinct rear, middle, side, and front responses to a single global migration stimulus. ![]() For instance, do cells within the same tissue interpret a global migration ‘command’ differently based on where they are in the tissue? Similarly, since no stimulus is permanent, what are the long-term effects of transient commands on collective cell dynamics? We investigate these questions by bioelectrically programming large epithelial tissues to globally migrate ‘rightward’ via electrotaxis. However, while various technologies exist to make individual cells migrate, translating these tools to control myriad, collectively interacting cells within a single tissue poses many challenges. The ability to program collective cell migration can allow us to control critical multicellular processes in development, regenerative medicine, and invasive disease. ![]()
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