Biophysical Society Conference | Tahoe 2022

Molecular Biophysics of Membranes

Monday Speaker Abstracts

PIEZO1 ON THE MOVE Medha M. Pathak 1 ; 1 University of California, Irvine, Dept. of Physiology & Biophysics, Irvine, CA, USA 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 mechanotransduction in native cellular conditions. We find that the mechanically-activated ion channel Piezo1 transduces cell-generated traction forces to regulate a variety of biological processes. We show that cellular traction forces generate spatially-restricted Piezo1 Ca 2+ flickers in the absence of externally-applied mechanical forces. However, Piezo1 channels are widely distributed on the cell surface and are mobile. Single particle tracking reveals a heterogeneity in the mobility behavior of individual channel puncta. We propose that Piezo1 Ca 2+ flickers allow spatial segregation of mechanotransduction events and that mobility allows channel molecules to efficiently respond to mechanical stimuli. MEMBRANE CURVATURE MEDIATED SUBCELLULAR DISTRIBUTION OF PIEZO1 Zheng Shi 1 ; 1 Rutgers University, Chemistry and Chemical Biology, Piscataway, NJ, USA Piezo1 is the bona fide mechanosensitive ion channel in mammalian cells, activated by local tension in the plasma membrane. The distribution of Piezo1 within a cell is essential for mechano-transduction, cell division and migration, and wound healing. However, the underlying principle that guides the subcellular distribution of Piezo1 is still unclear. Here, we show that membrane curvature serves as a general regulator of Piezo1 distribution in the plasma membrane of live cells, leading to strong depletion of Piezo1 on membrane protrusions such as filopodia. Quantifying the membrane curvature preference of Piezo1 leads to a direct estimation of the molecular size Piezo1 in live cell membranes. Chemical activation leads to increased density of Piezo1 on filopodia, independent of Ca 2+ , consistent with a flattened configuration of the channel upon activation. Furthermore, the curvature preference of Piezo1 inhibits filopodia formation and regulates important aspects of cellular development and dynamics.

13