Boundary-Shape Driven Transitions in Vortex and Oscillatory Dynamics of Confined Epithelial Cells

Abstract

Controlling the collective motion of epithelial cell populations is fundamental for understanding multicellular self-organization and for advancing tissue engineering. Under spatial confinement, cells are known to exhibit either vortex rotation or oscillatory motion depending on boundary geometry, but the mechanisms governing transitions between these states remain unclear. Here, we investigated the collective motion of MDCK cells confined within a doublet circular boundary, where the confinement aspect ratio, defined as the distance between the centers of two circles relative to their radius, can be tuned by varying the degree of overlap. When the overlap is large, cells form a stable vortex. Increasing the confinement aspect ratio destabilizes this vortex and induces oscillatory motion characterized by periodic reversals of migration direction, before ultimately transitioning into disordered dynamics. To elucidate the underlying mechanism, we developed simulations of self-propelled particles incorporating local alignment (LA) and contact inhibition of locomotion (CIL). The model successfully reproduced the experimentally observed transitions from vortices to oscillatory motion and further revealed that an appropriate balance between LA and CIL is critical for stabilizing vortex pairs with velocity reversals. Our findings demonstrate that the confinement aspect ratio serves as a minimal control parameter governing transitions in the collective dynamics of epithelial monolayers.