There are many mysteries about the biological processes behind human hearing, but with the help of cutting-edge scientific tools, researchers are beginning to uncover their secrets. A team at Ohio State University has now produced the first ever atomic-scale map of tiny wires inside our ears, providing us with unprecedented insight into a key mechanism of organs and how hearing loss can occur when something goes wrong.
A team of American scientists has pinpointed a protein that determines whether an embryonic hair cell matures into a healthy sensory cell in the inner ear. These cells, called hair cells, play an important role in our hearing, a finding that opens up promising new avenues for the treatment of hearing loss.
The new study by researchers at Ohio State University is based in part on this foundation. It focuses on microscopic hairs located at the top of these hair cells in the inner ear — more specifically, very thin filaments, called tip links, that connect to the tops of these micro-hairs. When sound vibrates through the ear, these ear-tip links stretch and open small channels, allowing positively charged ions to transmit electrical signals between the ear and brain so that we can hear the sound. This is a similar process that allows us to balance.
“If you don’t have cutting-edge links, you can’t hear sound or maintain balance,” said Marcos Sotomayol, lead author of the study. “They are essential.”
Scientists have previously produced low-resolution images of cutting-edge links and know that they are made up of a pair of proteins called cadherin-23 and protocadherin-15, which are associated with hereditary deafness. Now, a team at Ohio State University has isolated parts of these proteins and used X-ray crystallism to create cutting-edge link structures at atomic levels.
“Now that we can see the atoms, we can create physics-based images to see how these cutting-edge links respond to the power of sound generation,” Sotomayor said. “It tells us more about how this works and what happens when they stop working.”
One of the key insights gathered from these cutting-edge linked high-resolution images is a new understanding of how the cadherin-23 and protocadherin-15 proteins interact. Scientists have learned that they form a type of connection they describe as a “molecular handshake”, which is the key to hearing and balance that is thought to bring about hearing and balance.
The team was also able to simulate the complex dynamics of tip links, as sound vibrations washed them away, allowing them to see how they stretch and deform when opening ion channels. Ultimately, these new insights could help scientists and doctors learn more about why cutting-edge links fail and study ways to prevent this from happening.
“These structures also reveal cutting-edge link sites where mutations occur in hereditary deafness,” Sotomayor said. “So we can try to understand what happens to the tip link when these sites are mutated, not only by looking at the static structure, but also by looking at the simulated trajectory of the tip link response sound.”
The study was published in the Proceedings of the National Academy of Sciences.