Abstract
Piezo channels transduce mechanical stimuli into electrical and chemical signals to powerfully influence development, tissue homeostasis, and regeneration. Studies on Piezo1 have largely focused on transduction of “outside-in” mechanical forces, and its response to internal, cell-generated forces remains poorly understood. Here, using measurements of endogenous Piezo1 activity and traction forces in native cellular conditions, we show that cellular traction forces generate spatially-restricted Piezo1-mediated Ca2+ flickers in the absence of externally-applied mechanical forces. Although Piezo1 channels diffuse readily in the plasma membrane and are widely distributed across the cell, their flicker activity is enriched near force-producing adhesions. The mechanical force that activates Piezo1 arises from Myosin II phosphorylation by Myosin Light Chain Kinase. We propose that Piezo1 Ca2+ flickers allow spatial segregation of mechanotransduction events, and that mobility allows Piezo1 channels to explore a large number of mechanical microdomains and thus respond to a greater diversity of mechanical cues.
Highlights
Piezo channels transduce mechanical stimuli into electrical and chemical signals to powerfully influence development, tissue homeostasis, and regeneration
An alternative, nonperturbing method to monitor activation of Piezo[1] channels is imaging Ca2+ flux through the channel[7,36]. Using this approach in human neural stem/progenitor cells (hNSPCs), we previously found that traction forces elicit discrete, local, and transient Ca2+ microdomains or “flickers” from endogenous Piezo[1] channels in the absence of externally applied mechanical forces[7]
We previously reported Ca2+ flickers observed by total internal reflection fluorescence microscopy (TIRFM) imaging of hNSPCs in the absence of external mechanical stimulation[7]
Summary
Piezo channels transduce mechanical stimuli into electrical and chemical signals to powerfully influence development, tissue homeostasis, and regeneration. We propose that Piezo[1] Ca2+ flickers allow spatial segregation of mechanotransduction events, and that mobility allows Piezo[1] channels to explore a large number of mechanical microdomains and respond to a greater diversity of mechanical cues Cells both detect and generate mechanical forces, and integrate mechanical information with genetic and chemical cues to shape organismal morphology, growth, and homeostasis. Piezo channels were recently identified as a new family of excitatory mechanically activated channels[2,3] Due to their permeability to Ca2+ and other cations, Piezo channel activity generates chemical as well as electrical signals in response to mechanical stimuli, allowing them to regulate a wide variety of cellular processes. Using this approach in hNSPCs, we previously found that traction forces elicit discrete, local, and transient Ca2+ microdomains or “flickers” from endogenous Piezo[1] channels in the absence of externally applied mechanical forces[7]
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