Fluid shear magnitude, mechanical history and actin-sensitive coupling shape Piezo1 signalling

Tang, S. S.; Gheorghita, M.; Hansen, B.; Frattolin, J.; Kalyviotis, K.; Lam, A. J. Y.; Tupin, S.; De Abreu Queiros Osorio, L.; Boecker, J.; van Batenburg-Sherwood, J.; Moore, J. E.; Salem, V.; Pantazis, P.

doi:10.64898/2026.10.10.758220

bioRxiv · 10.64898/2026.10.10.758220

Fluid shear magnitude, mechanical history and actin-sensitive coupling shape Piezo1 signalling

Tang, S. S.·Gheorghita, M.·Hansen, B.·Frattolin, J.·Kalyviotis, K.·Lam, A. J. Y.·Tupin, S.·De Abreu Queiros Osorio, L.·Boecker, J.·van Batenburg-Sherwood, J.·Moore, J. E.·Salem, V.·Pantazis, P.

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Abstract

Mechanical forces shape cell behaviour, yet how Piezo1-associated responses encode force magnitude, recent mechanical history and cytoskeletal context under repeated fluid shear remains unclear. We combined defined fluid shear stress (FSS) with GenEPi, a genetically encoded reporter of Piezo1-proximal Ca2+ entry, in engineered XLGenEPi-HEK293T monolayers to resolve mechanically evoked responses at single-cell and population scales. GenEPi responses increased with FSS magnitude but showed diminishing response gain at higher shear. Repeated submaximal FSS produced history-dependent attenuation and reduced temporal coordination, with higher FSS accelerating the early phase of attenuation. Low-dose Latrunculin A, without significantly reducing bulk F-actin abundance, converted sustained FSS-evoked signalling into a brief, decay-dominated response while largely preserving peak responses to Yoda1. These findings show that Piezo1-associated signalling is shaped over minutes by force magnitude, recent mechanical history and actin-sensitive mechanical coupling, providing a quantitative framework for understanding mechanotransduction under sustained and repeated mechanical stimulation.

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Tang, S. S., Gheorghita, M., Hansen, B., Frattolin, J., Kalyviotis, K., Lam, A. J. Y., Tupin, S., De Abreu Queiros Osorio, L., Boecker, J., van Batenburg-Sherwood, J., Moore, J. E., Salem, V., Pantazis, P.. 2026-10-12. Fluid shear magnitude, mechanical history and actin-sensitive coupling shape Piezo1 signalling. https://doi.org/10.64898/2026.10.10.758220

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