Contribution of cell mechanics in promoting collective behavior for supracellular migration

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Project Summary Highly ordered, directed movement in collective cell migration is a result of the magnitude of coordination and communication that takes place at both the cellular and tissue level. In this proposal, we focus on understanding the mechanisms that contribute to the system behaving as a ‘collective’ to achieve such phenomenon. The cardiopharyngeal progenitors of the tunicate Ciona provide the simplest model of collective cell migration, with cohesive bilateral cell pairs polarizing and migrating between the ventral epidermis and trunk endoderm. Bernadskaya & Yue et al. 2021 found that the collective cell migration of Ciona exhibits supracellular characteristics; while each cell has the machinery to migrate individually, for successful development, the cells travel together and take on the identity of either the ‘leader’ or ‘trailer’. How this collective polarity is established and communicated between the two cells, and the type of information being exchanged, remains to be elucidated. We propose that this collective migration is driven by a “rear-engine” with supracellular polarity, as mechanical information flows from the trailer cell to the leader cell. We speculate that the cell:cell junction serves as a point of plasticity; preliminary work has shown that the junction has relatively low levels of actomyosin, allowing it to be under low tension and easily deformable. We hypothesize the two cells are utilizing cell shape – specifically the direction and degree of deformation at the cell:cell junction – and hydrostatic pressure as a method for mechanical coupling. To test our hypothesis, we will use in vivo images to reverse-engineer forces, extract force measurements, and build computational models of migration. Then, we will experimentally validate the role of the cell:cell junction as an information hub contributing to supracellular polarity, cytoskeletal organization, as well as force generation and transmission.