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.

Auditory mechanics of the tectorial membrane and the cochlear spiral

“…A recent model estimating the contribution of TM coupling on HB spontaneous oscillations [13*] can be used to predict that a system of three cooperative resonant HBs will increase by three-fold a putative HB-based cochlear amplifier. This hypothesis is further supported by data obtained from two transgenic mice with reduced OHC coupling: Col11a2 −/− mice, which lack collagen XI and have lower density of TM collagen bundles and smaller radial mechanical coupling [14]; and Tecta C1509G/+ , in which the TM contacts only one row of OHCs [15]. Accordingly, these mice have up to 50 dB auditory threshold elevations as measured by ABR or DPOAE [14,15].…”

Biophysical Mechanisms Underlying Outer Hair Cell Loss Associated with a Shortened Tectorial Membrane

“…These changes are predicted to alter the pattern of OHC stereociliary stimulation along the cochlear partition (Gavara and Chadwick 2009;Gu et al 2008;Gueta et al 2006Gueta et al , 2007Gueta et al , 2008Masaki et al 2010;Meaud et al 2010;Shoelson et al 2004). As well, this may represent a shift in the tonotopic map of the cochlea secondary to altered TM and OHC stiffness gradients (Choi and Oghalai 2008;Deo and Grosh 2004;Ghaffari et al 2007;He et al 2003;Liu and Neely 2009;Masaki et al 2009;Richter et al 2007;Sfondouris et al 2008;Stasiunas et al 2009) or reduced gain of the cochlear amplifier (Oghalai 2004a).…”

Basilar Membrane and Tectorial Membrane Stiffness in the CBA/CaJ Mouse

“…Experimental results are available that studied the micromechanics of the organ of Corti in excised cochlear preparations, including guinea pig temporal bone preparations, sections of the guinea pig, gerbil cochlea, and the gerbil hemicochlea (Chan and Hudspeth 2005;Edge et al 1998;Fridberger et al 2002a, b;Fridberger and de Monvel 2003;Hu et al 1995Hu et al , 1999Jacob et al 2011;Jia et al 2007;Karavitaki and Mountain 2007a, b;Karavitaki et al 1996;Mammano and Ashmore 1993;Morioka et al 1995;Nowotny and Gummer 2006;Reuter et al 1992;Dallos 2001, 2003;Richter et al 2002Richter et al , 2000von Tiedemann et al 2010). Results have been published using confocal microscopy or optical coherence tomography (OCT) to study micromechanics of the cochlea in vivo (Chen et al 2007(Chen et al , 2011Choudhury et al 2006;Gao et al 2011Gao et al , 2013Masaki et al 2009;Zha et al 2012).…”

“…The homologies between mice and human genomes are well-established, and the hereditary abnormalities are similar (Steel and Brown 1996;Zheng et al 1999). Such genetically induced abnormalities might manifest themselves in changes of physical properties of cochlear structures and thus result in abnormal cochlear mechanics and cochlear dysfunction (Legan et al 2000;Masaki et al 2009). For example, the mutation of the gene that encodes α-tectorin resulted in TM detachment from stereo cilia and disruption of its non-collagenous matrix (Legan et al 2000).…”