Tokushige, N. | bioRxiv Science

bioRxiv2026

Force transmission balance through adhesions determines multicellular handedness

Cell chirality has been implicated in left-right (LR) asymmetric morphogenesis, yet multicellular handedness is not a simple readout of single-cell chirality. Here, we show that multicellular LR asymmetry is determined by the balance of force transmission through cell-cell and cell-substrate adhesions. Combining experiments in human epithelial cells with theoretical modeling, we demonstrate that clockwise-rotating single cells can generate either clockwise or counterclockwise collective rotation depending on whether chiral forces are transmitted primarily through adherens junctions or focal adhesions, without altering single-cell chirality itself. Mechanistically, microtubules promoted junctional force transmission by recruiting the actin-microtubule crosslinker ACF7 to cell-cell contacts, where ACF7 stabilized F-actin and enabled intercellular mechanical coupling. Our results define a mechanical framework in which the routing of chiral forces through adhesions, rather than single-cell chirality alone, determines multicellular handedness.

cell biology↗

bioRxiv2023

Epithelial cell chirality emerges through the dynamic concentric pattern of actomyosin cytoskeleton

The chirality of tissues and organs is essential for their proper function and development. Tissue-level chirality derives from the chirality of individual cells that comprise the tissue, and cellular chirality is considered to emerge through the organization of chiral molecules within the cell. However, the principle of how molecular chirality leads to cellular chirality remains unresolved. To address this fundamental question, we experimentally studied the chiral behaviors of isolated epithelial cells derived from a carcinoma line and developed a theoretical understanding of how their behaviors arise from molecular-level chirality. We first found that the nucleus rotates and the cytoplasm circulates robustly in a clockwise direction. During the rotation, actin and myosin IIA are organized into stress fibers with a vortex-like chiral orientation at the ventral side of the cell periphery, simultaneously forming thin filaments with a concentric orientation at the dorsal level of the cell. Surprisingly, we found that the intracellular rotation is driven by the concentric pattern of actomyosin filaments on the dorsal surface of the cell, not by the vortex-like chiral stress fibers. To elucidate how the concentric actomyosin filaments induce chiral rotation, we analyzed a theoretical model developed based on the theory of active chiral fluid, and revealed that the observed cell-scale unidirectional rotation is driven by the molecular-scale chirality of actomyosin filaments even in the absence of cell-scale chiral orientational order. Our study thus provides novel mechanistic insights into how the molecular chirality is organized into the cellular chirality and an important step towards understanding left-right symmetry breaking in tissues and organs.

cell biology↗