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A major unanswered question in biology is how mechanical forces are generated, detected and transduced by cells to impact biochemical and genetic programs. Our work is aimed at uncovering the mechanical principles at play in cells and tissues using novel molecular, imaging and bioengineering tools. Here we present insights gleaned from non-invasive approaches to measure and manipulate mechanical signals in native cellular conditions. We find that the mechanically-activated ion channel Piezo1 transduces cell-generated traction forces to regulate a variety of physiological processes. We show that actomyosin-based cellular traction forces generate spatially-restricted Piezo1 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 Ca²⁺ flicker activity is enriched in regions proximal to force-producing adhesions. We propose that Piezo1 Ca²⁺ flickers allow spatial segregation of mechanotransduction events, and that mobility allows channel molecules to efficiently respond to local mechanical stimuli.

This seminar will be available both in-person and online, details in attached poster.