Cell jamming regulates epithelial chiral morphogenesis

Abstract

Internal organs such as the heart demonstrate apparent left-right (LR) asymmetric morphology and positioning. Cellular chirality and associated LR biased mechanical behavior such as cell migration have been attributed to LR symmetry breaking during embryonic development. Mathematical models have shown that chiral directional migration can be driven by cellular intrinsic torque. Tissue jamming state (i.e., solid-like vs fluid-like state) strongly regulates collective migratory behavior, but how it might affect chiral morphogenesis is still unknown. Here, we develop a cell vertex model to study the role of tissue rigidity or jamming state on chiral morphogenesis of the cells on a patterned ring-shaped tissue, simulating a previously reported experimental setup for measuring cell chirality. We simulate chirality as torsional forces acting on cell vertices. As expected, the cells undergo bidirectional migration at the opposing (inner and outer) boundaries of the ring-shaped tissue. We discover that more fluid-like tissues (unjammed) demonstrate a stronger chiral cell alignment and elongation than more solid-like (jammed) tissues and maintain a bigger difference in migration velocity between opposing tissue boundaries. Finally, we find that fluid-like tissues undergo more cell-neighbor exchange events. This study reveals that chiral torque is sufficient to achieve a biased cellular alignment as seen in vitro. It further sheds light on the mechanical regulation of chiral morphogenesis of tissues and reveals a role of cell density-independent tissue rigidity in this process.

Keywords: Cell chirality; Cell vertex model; Epithelium; Left–right asymmetry.