Myosin-II mediated traction forces evoke localized Piezo1-dependent Ca ²⁺ flickers

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 Ca ²⁺ 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 Ca ²⁺ 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.

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Ellefsen et al. monitor Piezo-dependent Calcium signals in live cells by TIRF and super-resolution microscopy and find that Ca ²⁺ flickers localize to areas of high traction force. They show that Myosin II activity and MLCK are needed for the generation of Piezo Ca ²⁺ signals and that Piezo1 channels are mobile in the plasma membrane.