Modeling and Simulation Group Meeting
Chirality in single cell and cell collectives as an emergent property of actin self-organization
Speaker: Wenzheng Shi, Courant Institute
Location: Warren Weaver Hall 1302
Date: Thursday, April 11, 2024, 12:30 p.m.
Synopsis:
Deviations from mirror symmetry in multicellular organisms are ubiquitous, yet the molecular mechanisms responsible for the symmetry-breaking remain largely unclear. We investigated the development of a chiral pattern in single cells and groups of cells confined to adhesive islands. Single cells on circular islands had actomyosin stress fibers arranged radially, like spokes on a wheel, tilted counterclockwise. When multiple cells were confined to a rectangular island, they elongated along one preferred diagonal and two long rectangle boundaries, making the Cyrillic letter И. Several knockdowns found to reverse stress fiber tilting clockwise in single cells caused multiple cell patterns to reverse chirality to the Roman letter N. To understand the origin of this chirality, we translated microscopy observations into computational models in which the dynamic stress fibers merge and align along the long axis of the cell, and then tilt relative to this axis in a chiral way; neighboring cells tend to align with each other, and cells align with the adhesive boundary.
Simulations of several variants of this model and comparison with experiments based on model predictions revealed that the collective chirality arises from the cells interacting with the boundary, and not from the cell-cell interactions inside the cell group. The resulting model successfully reproduced all observed experimental patterns on the islands of many shapes and sizes. Lastly, we mixed cells of opposite chirality, which led to intricate patterns dependent on the density ratio between these cell types. Our results suggest a novel pathway of chirality propagation from subcellular to multicellular scale underscored by stress fiber dynamics and geometry of the multicellular environment.