Computational Modeling of the Stereocilia Plasma Membrane

Abstract

Stereocilia are hair-like bundles found in the inner ear that are primarily responsible for the mechanosensory transduction mechanisms that allow us to hear and interpret sound. Stereocilia possess tip links with tension-gated ion channels, which when opened translocate Ca²⁺ ions, resulting in a depolarization event that triggers signal transmission to the cochlear nerve. Degeneration of the stereocilia structure interferes with this complex process, potentially leading to non-syndromic hearing loss. As such, there has been a focus on understanding the mechanical properties of its lipid bilayer important to mechanosensory transduction and providing model stereocilia membranes for future study. We aim to do this through the development and simulation of an asymmetric model stereocilia bilayer, using molecular dynamics with the CHARMM36 all-atom lipid force field. In studying the different biophysical membrane properties between symmetric and asymmetric model membranes, we observe increases in hydrogen bonding potential, changes in lipid headgroup lateral clustering patterns, and electron density profiles that could propagate stability in the asymmetric model membrane. We aim to apply this to understand the compositions or states of the stereocilia plasma membrane, which could play a role in the complex mechanotransduction pathway.