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bioRxiv · 10.64898/2026.04.04.716462

Force transmission balance through adhesions determines multicellular handedness

Ishibashi, T.·Nishizawa, R.·Ogita, G.·Tokushige, N.·Shibata, T.
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Abstract

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.

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Ishibashi, T., Nishizawa, R., Ogita, G., Tokushige, N., Shibata, T.. 2026-04-07. Force transmission balance through adhesions determines multicellular handedness. https://doi.org/10.64898/2026.04.04.716462

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