Membrane scaffolding in auditory hair cells - a molecular tightrope walk enables lateral wall stiffness and...

The mammalian cochlea achieves remarkable sensitivity and frequency selectivity through the coordinated function of sensory inner hair cells (IHCs) and electromotile outer hair cells (OHCs). OHCs play a critical role in cochlear amplification by converting changes in membrane voltage into rapid mechanical length changes through a process known as electromotility. This active mechanical feedback enhances basilar membrane motion and sharpens auditory frequency tuning. The structural basis enabling these dynamic mechanical responses lies in the specialized trilaminate architecture of the OHC lateral wall, consisting of (i) the plasma membrane, which harbors the motor protein prestin, (ii) the actin/spectrin-based cortical lattice and (iii) the subsurface cisternae. Prestin densely populates the plasma membrane and generates membrane area changes that drive reversible axial cell contraction. Beneath the membrane, a spectrin-crosslinked actin lattice provides both flexibility and mechanical resilience, enabling controlled longitudinal deformation during electromotile cycles. However, several aspects of this system remain unresolved, including the precise spectrin isoform composition, the molecular identity of membrane/cytoskeleton connectors (so-called 'pillars'), and the functional role of the subsurface cisternae. This review summarizes current knowledge of OHC electromotility and lateral wall architecture while identifying key open questions necessary to fully understand the cellular mechanisms underlying cochlear amplification.