[5] PIEZO1 is a large mechanosensitive ion channel protein that forms a homotrimeric complex with a distinctive three-bladed, propeller-shaped architecture.

It can be directly activated by membrane tension, with the peripheral blade and beam structures likely acting as mechanotransduction modules.

When activated, a lever-like mechanogating mechanism is assumed for the flexible blades, opening the central pore to allow for the influx of calcium ions.

[12] Potassium and chloride ions are expelled in this process to restore osmotic balance, creating a gradient that encourages water to move out of the cell.

[12][14] In dorsal root ganglia (DRG), Piezo1 enables cells to detect substrate stiffness and modulate behavior through the calpain-integrin-E-cadherin pathway.

[15] Beginning with the activation of calpain, a protease that modulates the cytoskeleton and E-cadherin, this pathway affects integrin B1, a receptor of extracellular matrix proteins.

Piezo1 signaling ensures the proper localization to facilitate cell-matrix adhesion, cellular aggregation, and balance between proliferation with apoptosis.

[13][16] Additionally, Piezo1 can affect the Hippo/YAP pathway, which controls cell proliferation and differentiation, underscoring Piezo1’s role in cellular metastasis.

[17] With this knowledge, further research is needed to investigate the inhibition of tumor progression that therapeutic targeting potentially offers.

This mechanism is independent from direct protein interaction, but is still critical in modulating local ion channels and signaling cascades.

[9] Consequently Piezo1 plays a significant role in multiple neurobiological processes including axon regeneration, neural stem cells differentiation and neurological diseases progression.

This acts to prevent excess proliferation of skin tissue, and has been implicated in cancer biology as a contributing factor to metastases by assisting living cells in escaping from a monolayer.

[29] Expression of murine Piezo1 in mouse innate immune cells is essential for their function, a role mediated by sensing mechanical cues.

Microglial maintenance cells, which express Piezo1, detect this stiffness via Piezo1-enabled mechanosensation and in response surround, compact, and phagocytosize the plaques.