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

Researchers have discovered how mechanical forces influence Piezo1-associated responses within cells, shedding light on the factors that shape these mechanical signals. Utilizing a genetically encoded Piezo1-proximal calcium entry reporter called GenEPi, scientists systematically examined the effects of defined fluid shear stress (FSS) on single-cell and population-level Piezo1 responses in engineered monolayers of HEK293T cells.

The findings revealed that Piezo1 responses are heightened by stronger FSS magnitudes, but the response gain starts to diminish at higher shear forces. Additionally, when cells experience repeated submaximal FSS, the mechanical history results in attenuated responses and reduced temporal coordination, with a higher FSS accelerating the early phase of this attenuation.

Interestingly, even low doses of the drug Latrunculin A, which does not significantly reduce the overall amount of F-actin, can convert prolonged FSS-evoked signaling into a brief, decay-dominated response while preserving the peak responses to another stimulus called Yoda1. These results demonstrate that Piezo1-associated signaling is not only influenced by force magnitude but also by the cell's recent mechanical history and actin-sensitive mechanical coupling.

The study provides a quantitative framework for understanding how cells transduce mechanical stimuli into biochemical signals over minutes of sustained or repeated mechanical stimulation.