Mechanistic integration of mechanical forces generating chiral bias in confined endothelial cell doublets

Establish a mechanistic explanation for how mechanical forces, including cell polarity, cell–cell interactions (e.g., volume exclusion/repulsion), and geometric confinement to circular fibronectin-coated micropatterns, integrate to generate chiral (clockwise versus counterclockwise) rotational bias in pairs of endothelial cells.

Background

Recent experiments on human umbilical vein endothelial cell (HUVEC) doublets confined to circular fibronectin-coated islands revealed persistent rotations with a mild clockwise bias that can be amplified or reversed by modulating contractility. Despite these observations, it has not been clear which macroscopic forces and interactions distinguish left from right or how they combine to produce a directional bias.

The paper introduces a minimal model incorporating polarity, confinement, and pairwise repulsion to reproduce observed behaviors, but explicitly notes that a mechanistic understanding of how these forces integrate to yield chiral bias had remained unresolved, motivating the modeling and analysis presented.