Outer hair cell electromechanics as a problem in soft matter physics: Prestin, the membrane and the cytoskeleton

The electromechanical coupling exhibited by cochlear outer hair cells is a remarkable biophysical phenomenon. These specialized cells generate forces at acoustic frequencies and enable high-frequency hearing in mammals. While there has been significant progress since the discovery of electromotility - including the discovery of the motor protein prestin - we still do not have a clear picture of how electromotility works. A particularly vexing problem is how forces, generated by a membrane-based motor, are rapidly transmitted to the underlying cytoskeleton to enable force generation on the microsecond time scales required for amplification of acoustic signals. Here we approach the problem of electromotility from the perspective of soft matter physics in light of recent ultrastructural findings from 3D electron tomography studies on outer hair cells immobilized by high-pressure freezing. We then survey our understanding of prestin-membrane and prestin-cytoskeletal interactions in the context recently published cryoelectron microscopy (cryo-EM) structures of prestin. This will lead to the proposal of a new conceptual model of electromotility consistent with conformational states observed in the pillar proteins and actin filaments. This article is part of the Special Issue Outer hair cell Edited by Joseph Santos-Sacchi and Kumar Navaratnam.