PROJECT SUMMARY The long-term objective of this project is to understand how an ion channel called Piezo1 endows living cells with the ability to sense mechanical forces in their environment. This ability underlies a wide range of physiological processes that are essential to life, including the control of cell size and shape, the coalescence of cells into an organ system, and blood pressure control. The experiments are designed on the principle that to understand we must first see what Piezo1 looks like in its various forms. To this end the electron microscope will be used. We must also observe the functional properties of Piezo1 under conditions in which we understand every component present. Then, by comparing the functional properties, that is, how much the channel opens and closes under known quantities of applied force, with the structures, we can construct a physics-based model to explain the observable properties of Piezo1. Because we know that biology is complex, in a final stage of this project we aim to determine structures of Piezo1 in the cell membrane. There, we cannot yet know all the components that are present, but we hope to further understand how the more complex environment of the cell regulates the behavior of Piezo1.