Lipid-mediated prestin organization in outer hair cell membranes and its implications in sound amplification

Prestin is a high-density motor protein in the outer hair cells (OHCs), whose conformational response to acoustic signals alters the shape of the cell, thereby playing a major role in sound amplification by the cochlea. Despite recent structures, prestin's intimate interactions with the membrane, which are central to its function remained unresolved. Here, employing a large set (collectively, more than 0.5 ms) of coarse-grained molecular dynamics simulations, we demonstrate the impact of prestin's lipid-protein interactions on its organization at densities relevant to the OHCs and its effectiveness in reshaping OHCs. Prestin causes anisotropic membrane deformation, which mediates a preferential membrane organization of prestin where deformation patterns by neighboring copies are aligned constructively. The resulting reduced membrane rigidity is hypothesized to maximize the impact of prestin on OHC reshaping. These results demonstrate a clear case of protein-protein cooperative communication in membrane, purely mediated by interactions with lipids.