Cell chirality reversal through tilted balance between polymerization of radial fibers and clockwise-swirling of transverse arcs

Cell chirality is an intrinsic property characterized by biased cell rotation or orientation. Although the importance of the right-handed double helix of actin is known, how a single form of molecular handedness manifests diverse forms of cell chirality remains unclear. Here, we found that the cell nucleus rotated with a clockwise (CW) bias in a small projected area, but this rotation reversed to an anticlockwise (ACW) bias as cell spreading increased. Actin analysis suggested that radial fiber polymerization accounts for the ACW bias. Alterations in transverse arc components (myosin II, mDia2, and tropomyosin 4) revealed that the CW bias is driven by the retrograde flow, originating from the tethered gliding motion of myosin II in the contractile structure of transverse arcs. Thus, an imbalance between radial fibers and transverse arcs results in cell chirality reversal. The findings elucidate the mechanisms underlying cell chirality reversal, providing a new perspective on mechanobiology. © 2023, Kwong et al.