Poster abstracts
Poster number 40 submitted by Collin Nisler
Simulating the mechanotransduction complex with coarse-grain molecular dynamics
Collin Nisler (Biophysics)
Abstract:
Hearing is an ubiquitous and conserved process that endows animals with an astonishingly sensitive means to sense the environment. This is achieved through a sensitivity to sound or water pressure waves which are transmitted to the inner ear. In the inner ear, the perturbations from this mechanical stimulus are converted to an action potential that is interpreted by the brain as sound. This process is known as mechanotransduction, and relies on the interaction of two proteins found in the inner ear, protocadherin 15 (PCDH15) and cadherin 23 (CDH23). The transmembrane region of PCDH15 then forms a multi-protein complex at the cell membrane composed of tetraspan membrane protein of hair cell stereocilia (TMHS), transmembrane inner ear protein (TMIE), and the cation selective ion channels, transmembrane channel-like (TMC) 1 and 2. While structures of TMHS have been solved with cryo-electron microscopy, and models of TMC have been built using homology modeling methods, how these proteins interact with one another, and thus how the force is transmitted from Pcdh15 to the ion channel, remains unknown. Here, coarse-grain molecular dynamics is used to model this complex of proteins in the cell membrane and to sample long timescales in which interactions between these proteins are observed. Already, long equilibrium simulations show a repeatable interaction between TMIE and PCDH15, with ongoing simulations similarly testing PCDH15, TMIE, and TMHS, as well as TMIE with TMC1. A model of the mechanotransduction channel complex can then be proposed from these results, which can serve as a guide for experimental testing.
Keywords: Mechanotransduction, Molecular Dynamics, Computational Modeling