Mechanosensitivity of Coupled Active Hair-Cell Bundles

Abstract

Mechanosensation is the process by which cells sense mechanical forces and translate them into electrical and chemical signals. Important physiological functions including sensation of touch, sensation of sound and proprioception are based on mechanosensation. Recent studies identified the molecular identity of a highly conserved group of mechanosensitive receptors, called Piezo receptors, which are both necessary and sufficient for cells to sense force. Currently, structure-function information of Piezo receptors is limited, and the mechanism how these receptors sense force, which conformational changes they undergo, and which precise mechanical stimuli cause these channels to open, remains poorly understood. Studies to date have used rather brute forces reaching several hundrets of nano-Newton to mechanically activate Piezo channels, which are likely too high to be of specific nature. To manipulate Piezo receptors at high precision and accuracy in a cellular context, new techniques have to be applied. We are currently developing assays to investigate Piezo receptors at the molecular level with delicate force control. Using a combination of high-resolution atomic force microscopy (AFM) and time-lapse fluorescent calcium imaging, we aim to find more effi