We seek to understand how hearing works at a molecular level; that is, how a sound wave is transduced into an electrical signal by hair cells of the inner ear. The cover image of the March 17 issue of Biophysical Journal shows a mouse cochlea that has been immunostained to reveal features that are important for hearing.

Hair bundles, shown in white, are decorated with red puncta corresponding to the tip-link protein PCDH15. PCDH15 is a component of the mechanosensory transduction (MT) complex, which converts the mechanical stimulus of a sound wave into an electrical signal. This confocal image highlights the scarcity of the MT complex in the inner ear, which is one of the central challenges in this field of study and the major driver for the development of ultrasensitive methods presented in this research article.

In this work, we optimized two ultrasensitive methods, single-molecule pull-down and single-molecule array, and demonstrated that they can be used to quantitate and characterize the MT subunits PCDH15 and LHFPL5. These methods are broadly applicable to similarly scarce proteins in other organisms and tissues. You can find more information about our work at https://www.ohsu.edu/gouaux-lab.

— Sarah Clark, Jaba Mitra, Johannes Elferich, April Goehring, Jingpeng Ge, Taekjip Ha, and Eric Gouaux