title: Col11a2 deletion reveals the molecular basis for tectorial membrane mechanical anisotropy.
abstract: The tectorial membrane (TM) has a significantly larger stiffness in the radial direction than other directions, a prominent mechanical anisotropy that is believed to be critical for the proper functioning of the cochlea. To determine the molecular basis of this anisotropy, we measured material properties of TMs from mice with a targeted deletion of Col11a2, which encodes for collagen XI. In light micrographs, the density of TM radial collagen fibers was lower in Col11a2 -/- mice than wild-types. Tone-evoked distortion product otoacoustic emission and auditory brainstem response measurements in Col11a2 -/- mice were reduced by 30-50 dB independent of frequency as compared with wild-types, showing that the sensitivity loss is cochlear in origin. Stress-strain measurements made using osmotic pressure revealed no significant dependence of TM bulk compressibility on the presence of collagen XI. Charge measurements made by placing the TM as an electrical conduit between two baths revealed no change in the density of charge affixed to the TM matrix in Col11a2 -/- mice. Measurements of mechanical shear impedance revealed a 5.5 +/- 0.8 dB decrease in radial shear impedance and a 3.3 +/- 0.3 dB decrease in longitudinal shear impedance resulting from the Col11a2 deletion. The ratio of radial to longitudinal shear impedance fell from 1.8 +/- 0.7 for TMs from wild-type mice to 1.0 +/- 0.1 for those from Col11a2 -/- mice. These results show that the organization of collagen into radial fibrils is responsible for the mechanical anisotropy of the TM. This anisotropy can be attributed to increased mechanical coupling provided by the collagen fibrils. Mechanisms by which changes in TM material properties may contribute to the threshold elevation in Col11a2 -/- mice are discussed.
authors.affiliation: Harvard-MIT Division of Health Sciences and Technology and Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Kinuko
authors.initials: K
authors.lastname: Masaki
authors.forename: Jianwen Wendy
authors.initials: JW
authors.lastname: Gu
authors.forename: Roozbeh
authors.initials: R
authors.lastname: Ghaffari
authors.forename: Gary
authors.initials: G
authors.lastname: Chan
authors.forename: Richard J H
authors.initials: RJ
authors.lastname: Smith
authors.forename: Dennis M
authors.initials: DM
authors.lastname: Freeman
authors.forename: A J
authors.initials: AJ
authors.lastname: Aranyosi
mesh_terms: D000818:Animals; D016880:Anisotropy; D001309:Auditory Threshold / Q000502:physiology; D003051:Cochlea / Q000502:physiology; D003094:Collagen / Q000235:genetics / Q000502:physiology*; D024161:Collagen Type XI / Q000235:genetics*; D004548:Elasticity; D016057:Evoked Potentials, Auditory, Brain Stem / Q000235:genetics / Q000502:physiology; D017353:Gene Deletion; D051379:Mice; D018345:Mice, Knockout; D008839:Microelectrodes; D013314:Stress, Mechanical; D013680:Tectorial Membrane / Q000502:physiology*
chemical_list: C497046:Col11a2 protein, mouse; D024161:Collagen Type XI; D003094:Collagen