The sensations of touch and hearing, along with many other physiological processes, require cells to be able to sense and react to mechanical stimuli. One way this is done is via membrane embedded mechanically gated channels. These channels can detect forces through deformation of the lipid bilayer, deemed the “force-from-lipids” principle. Bacterial homologues, such as MscL and MscS, exemplify this principle and have been studied for the past couple of decades, and have contributed greatly to our understanding of mechanically gated channels. However, understanding the underlying molecular force sensing mechanisms, and how similar bacterial and eukaryotic mechanosensitive channels are in terms of their gating mechanisms, remains an open question.
The recent discovery and structure elucidation of the first eukaryotic mechanically gated channels, named the PIEZO family, allows for the mechanisms of mechanical gating to be studied in higher organisms. Since their discovery, PIEZO channels have been implicated in many cellular processes, but the gating mechanism and the role that lipids play in PIEZO’s mechanics remain elusive. To this end, we are using a combination of electrophysiology and molecular simulations to understand protein-lipid interactions between Piezo1 and relevant lipids in model mammalian bilayers, and ultimately the role that lipids have on Piezo1’s activation. We are able to show that piezo has specific interactions with a number of membrane components that likely play a role in mediating the bilayer-protein interaction.