Essential mechanosensory functions such as touch and proprioception are mediated by PIEZO2, a mechanosensitive ion channel that converts mechanical force into electrical signals. Despite progress in understanding the physiological roles of PIEZO2, very little is known about how the channel functions at a molecular level. This project will use single-molecule in-situ fluorescence nanoscopy and electrophysiology to determine the molecular movements that underlie channel activation and inhibition. These data will reveal how PIEZO2 is tuned to detect sensory stimuli.