Emergence of slip-ideal-slip behavior in tip-links serve as force filters of sound in hearing

Nisha Arora, Jagadish P. Hazra, Sandip Roy, Gaurav K. Bhati, Sarika Gupta, K. P. Yogendran, Abhishek Chaudhuri (), Amin Sagar () and Sabyasachi Rakshit ()
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Nisha Arora: Indian Institute of Science Education and Research Mohali
Jagadish P. Hazra: Indian Institute of Science Education and Research Mohali
Sandip Roy: Indian Institute of Science Education and Research Mohali
Gaurav K. Bhati: Indian Institute of Science Education and Research Mohali
Sarika Gupta: National Institute of Immunology
K. P. Yogendran: Indian Institute of Science Education and Research Mohali
Abhishek Chaudhuri: Indian Institute of Science Education and Research Mohali
Amin Sagar: Université de Montpellier
Sabyasachi Rakshit: Indian Institute of Science Education and Research Mohali

Nature Communications, 2024, vol. 15, issue 1, 1-13

Abstract: Abstract Tip-links in the inner ear convey force from sound and trigger mechanotransduction. Here, we present evidence that tip-links (collectively as heterotetrameric complexes of cadherins) function as force filters during mechanotransduction. Our force-clamp experiments reveal that the tip-link complexes show slip-ideal-slip bond dynamics. At low forces, the lifetime of the tip-link complex drops monotonically, indicating slip-bond dynamics. The ideal bond, rare in nature, is seen in an intermediate force regime where the survival of the complex remains constant over a wide range. At large forces, tip-links follow a slip bond and dissociate entirely to cut-off force transmission. In contrast, the individual tip-links (heterodimers) display slip-catch-slip bonds to the applied forces. While with a phenotypic mutant, we showed the importance of the slip-catch-slip bonds in uninterrupted hearing, our coarse-grained Langevin dynamics simulations demonstrated that the slip-ideal-slip bonds emerge as a collective feature from the slip-catch-slip bonds of individual tip-links.

Date: 2024
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DOI: 10.1038/s41467-024-45423-8

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