Fluid shear magnitude, mechanical history and actin-sensitive coupling shape Piezo1 signalling
- 1Imperial College London
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.
Related
- Reciprocal coupling between EMT and BMP morphogen signalling drives collective cell invasion
- Viscous mechanical cues encode metastatic behavior through cytoskeletal-nuclear coupling and chromatin remodeling
- Mechanical coupling narrows an epithelial colony before it reaches a bottleneck
- Cancer-associated fibroblasts in head and neck tumours: signalling networks and therapeutic implications with insights from vestibular schwannoma
- Spatio-temporal modelling of the Hes1 and p53-Mdm2 intracellular signalling pathways
BibTeX
@misc{tang2026fluid,
title = {{Fluid shear magnitude, mechanical history and actin-sensitive coupling shape Piezo1 signalling}},
author = {S. S. Tang and M. Gheorghita and B. Hansen and J. Frattolin and K. Kalyviotis and A. J. Y. Lam and S. Tupin and L. De Abreu Queiros Osorio and J. Boecker and J. van Batenburg-Sherwood and J. E. Moore and V. Salem and P. Pantazis},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.10.758220},
url = {https://www.biorxiv.org/content/10.64898/2026.10.10.758220v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Fluid shear magnitude, mechanical history and actin-sensitive coupling shape Piezo1 signalling
AU - S. S. Tang
AU - M. Gheorghita
AU - B. Hansen
AU - J. Frattolin
AU - K. Kalyviotis
AU - A. J. Y. Lam
AU - S. Tupin
AU - L. De Abreu Queiros Osorio
AU - J. Boecker
AU - J. van Batenburg-Sherwood
AU - J. E. Moore
AU - V. Salem
AU - P. Pantazis
PY - 2026
DA - 2026/10/10
PB - bioRxiv
DO - 10.64898/2026.10.10.758220
UR - https://www.biorxiv.org/content/10.64898/2026.10.10.758220v1
AB - 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.
ER -