School of Physics Soft Condensed Matter & Biophysics: Prof. Marcos Sotomayor, Ohio State University

The senses of hearing and balance use hair cells of the inner ear to transform mechanical stimuli into electrical signals that can be processed in the brain. Mechanical force from sound or head movement is conveyed directly to hair-cell transduction ion channels by tip links, fine filaments formed by two atypical cadherins: protocadherin-15 and cadherin-23. These two proteins are required for mechanotransduction, are product of deafness genes, and feature long extracellular domains that interact tip-to-tip in a calcium-dependent manner. I will present our recent characterization of the cadherin-23 and protocadherin-15 bond using X- ray crystallography, microsecond-long molecular dynamics simulations, and biophysical experiments. Overall, our studies shed light on the molecular mechanics of hair-cell sensory transduction and may help in developing tailored treatments for cadherin-dependent deafness. Furthermore, the architecture of the protocadherin-15 and cadherin-23 complex reveals new interaction mechanisms for cadherins, a large protein family implicated in tissue and organ morphogenesis, neuronal connectivity, and cancer.