Penultimate author

Hair cells in the cochlea allow us to hear by converting sound waves into electrical impulses. But how they do this, and the molecules that govern the mechanics of the process, is not known. Ulrich Müller at the Scripps Research Institute in La Jolla, California, and his colleagues define a key hair-cell structure on page 87. He spoke to Nature about unravelling mechanotransduction.

We've had molecular descriptions of vision for some time, why not for hearing?

Vision, taste, smell and pain all rely on the action of ion channels, which have been well characterized. Hearing and touch rely on mechanically gated channels. At the tip of each hair cell is a bundle of stereocilia. The leading model posits that these are connected to each other by structures known as tip links, and that when tip links are deflected by sound pressure they exert a force that opens a spring-gated channel. But the molecules making up the tip link, spring and channel were unknown. We identified two molecules — cadherin 23 and protocadherin 15 — that interact to form tip links.

Why has tip-link structure been so elusive?

Because there are so few hair cells, their components cannot be purified using classical biochemical techniques. And tip links are so small that they are at the limit of microscope resolution.

What inspired you to search for the tip-link components, and where did you start?

Deafness is the most common form of sensory impairment in humans, yet our mechanical senses are the least well understood. We started by looking at genes linked to deafness, such as those for cadherin 23 and protocadherin 15, because it was possible they encoded components of the mechanotransduction machinery.

Where else is mechanotransduction important?

Mechanical phenomena occur throughout the body, having roles in features as diverse as posture, blood-pressure control and embryonic development. Understanding mechanotransduction is a major challenge. Knowing how biological components fit together and which are static and elastic has applications for nanotechnology and engineering.

What attracted you to hair-cell research?

The sheer beauty of these cells is amazing. I am also fascinated by their potential for mapping circuits in the brain. We know all the frequencies that stimulate these cells, so we can ask how a sound elicits a state of anxiety, fear, or joy in an animal.