Single-molecule force spectroscopy reveals the dynamic strength of the hair-cell tip-link connection.

Autor: Mulhall EM; Department of Neurobiology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.; Program in Neuroscience, Harvard University, Cambridge, MA, USA., Ward A; Department of Neurobiology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA., Yang D; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA., Koussa MA; Department of Neurobiology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.; Program in Neuroscience, Harvard University, Cambridge, MA, USA., Corey DP; Department of Neurobiology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA. dcorey@hms.harvard.edu., Wong WP; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA. wesley.wong@childrens.harvard.edu.; Department of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA. wesley.wong@childrens.harvard.edu.; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA. wesley.wong@childrens.harvard.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2021 Feb 08; Vol. 12 (1), pp. 849. Date of Electronic Publication: 2021 Feb 08.
DOI: 10.1038/s41467-021-21033-6
Abstrakt: The conversion of auditory and vestibular stimuli into electrical signals is initiated by force transmitted to a mechanotransduction channel through the tip link, a double stranded protein filament held together by two adhesion bonds in the middle. Although thought to form a relatively static structure, the dynamics of the tip-link connection has not been measured. Here, we biophysically characterize the strength of the tip-link connection at single-molecule resolution. We show that a single tip-link bond is more mechanically stable relative to classic cadherins, and our data indicate that the double stranded tip-link connection is stabilized by single strand rebinding facilitated by strong cis-dimerization domains. The measured lifetime of seconds suggests the tip-link is far more dynamic than previously thought. We also show how Ca 2+ alters tip-link lifetime through elastic modulation and reveal the mechanical phenotype of a hereditary deafness mutation. Together, these data show how the tip link is likely to function during mechanical stimuli.
Databáze: MEDLINE
Externí odkaz: