title: The local forces acting on the mechanotransduction channel in hair cell stereocilia.
abstract: In hair cells, mechanotransduction channels are located in the membrane of stereocilia tips, where the base of the tip link is attached. The tip-link force determines the system of other forces in the immediate channel environment, which change the channel open probability. This system of forces includes components that are out of plane and in plane relative to the membrane; the magnitude and direction of these components depend on the channel environment and arrangement. Using a computational model, we obtained the major forces involved as functions of the force applied via the tip link at the center of the membrane. We simulated factors related to channels and the membrane, including finite-sized channels located centrally or acentrally, stiffness of the hypothesized channel-cytoskeleton tether, and bending modulus of the membrane. Membrane forces are perpendicular to the directions of the principal curvatures of the deformed membrane. Our approach allows for a fine vectorial picture of the local forces gating the channel; membrane forces change with the membrane curvature and are themselves sufficient to affect the open probability of the channel.
authors.affiliation: Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Powers
authors.affiliation: Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Sue
authors.initials: S
authors.lastname: Kulason
authors.affiliation: Department of Microbiology, Columbia University, New York, New York.
authors.forename: Erdinc
authors.initials: E
authors.lastname: Atilgan
authors.affiliation: Bobby R. Alford Department of Otolaryngology-Head & Neck Surgery, Baylor College of Medicine, Houston, Texas.
authors.forename: William E
authors.initials: WE
authors.lastname: Brownell
authors.affiliation: Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland; Department of Mechanical Engineering, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Sean X
authors.initials: SX
authors.lastname: Sun
authors.affiliation: Oregon Hearing Research Center and Vollum Institute, Oregon Health & Science University, Portland, Oregon.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Barr-Gillespie
authors.affiliation: Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland; Department of Mechanical Engineering, Johns Hopkins University, Baltimore, Maryland. Electronic address: aspector@jhu.edu.
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Spector
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D006198:Hair Cells, Auditory / Q000378:metabolism; D018069:Hair Cells, Vestibular / Q000378:metabolism; D006801:Humans; D040542:Mechanotransduction, Cellular; D008954:Models, Biological; D059547:Stereocilia / Q000378:metabolism*