Deformable Particle Modeling Reveals How Cell Shape Dynamics Govern Collective Cell Motion

Collective cell migration involves cell motion in which cell-cell contacts are maintained. Collective cell dynamics can occur in two regimes: one in which cell-substrate tension>>cell-cell tension, and another in which cell-cell tension >> cell-substrate tension. In the former, cells exist as monolayers, whereas in the latter, they form three-dimensional aggregates. However, the relationship between cell shape and motion in both of these regimes remains poorly understood. We first model collective motion in the monolayer regime, where cell–substrate tension dominates, using a deformable particle model that allows each cell to dynamically adjust its preferred perimeter in response to local forces. In this model, cell shape emerges as an output of cell motion rather than being a mechanical input. Remarkably, the model reproduces the experimentally observed, broad and skewed shape parameter distribution P(S) of epithelial cells, where S = P²/4πA and P and A are the perimeter and area of a cell, respectively.  Moreover, the steady state shape distribution is an emergent property, rather than a function of the initial shape parameters we choose in our model. We thus conclude that epithelial cells dynamically adapt their preferred shape parameters during motion. We then examine the aggregate regime, where cell-cell tension dominates. Using adhesive deformable particles,  we generate cell spheroids exhibiting strain that increases radially from the center to the periphery. Upon locally releasing tension, the system reproduces toroidal Marangoni flows observed experimentally. These results reveal that surface tension in cell aggregates arises due to a radially increasing cellular strain, which in turn correlates with the cell shape parameter . Thus, our modeling provides a unified framework linking cell shape, strain, surface tension, and motion across the two regimes of collective migration.