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1.
Biophys J ; 111(5): 921-4, 2016 Sep 06.
Article in English | MEDLINE | ID: mdl-27544000

ABSTRACT

Our ability to understand speech requires neural tuning with high frequency resolution, but the peripheral mechanisms underlying sharp tuning in humans remain unclear. Sharp tuning in genetically modified mice has been attributed to decreases in spread of excitation of tectorial membrane traveling waves. Here we show that the spread of excitation of tectorial membrane waves is similar in humans and mice, although the mechanical excitation spans fewer frequencies in humans-suggesting a possible mechanism for sharper tuning.


Subject(s)
Hearing/physiology , Tectorial Membrane/physiology , Animals , Biomechanical Phenomena , Humans , In Vitro Techniques , Mice , Motion , Physical Stimulation , Sound , Species Specificity , Speech Perception/physiology , Viscosity
2.
Proc Natl Acad Sci U S A ; 112(42): 12968-73, 2015 Oct 20.
Article in English | MEDLINE | ID: mdl-26438861

ABSTRACT

The mammalian inner ear separates sounds by their frequency content, and this separation underlies important properties of human hearing, including our ability to understand speech in noisy environments. Studies of genetic disorders of hearing have demonstrated a link between frequency selectivity and wave properties of the tectorial membrane (TM). To understand these wave properties better, we developed chemical manipulations that systematically and reversibly alter TM stiffness and viscosity. Using microfabricated shear probes, we show that (i) reducing pH reduces TM stiffness with little change in TM viscosity and (ii) adding PEG increases TM viscosity with little change in TM stiffness. By applying these manipulations in measurements of TM waves, we show that TM wave speed is determined primarily by stiffness at low frequencies and by viscosity at high frequencies. Both TM viscosity and stiffness affect the longitudinal spread of mechanical excitation through the TM over a broad range of frequencies. Increasing TM viscosity or decreasing stiffness reduces longitudinal spread of mechanical excitation, thereby coupling a smaller range of best frequencies and sharpening tuning. In contrast, increasing viscous loss or decreasing stiffness would tend to broaden tuning in resonance-based TM models. Thus, TM wave and resonance mechanisms are fundamentally different in the way they control frequency selectivity.


Subject(s)
Tectorial Membrane/physiology , Animals , Cochlea/physiology , Models, Biological , Viscosity
3.
Biophys J ; 106(6): 1406-13, 2014 Mar 18.
Article in English | MEDLINE | ID: mdl-24655516

ABSTRACT

Cochlear frequency selectivity plays a key role in our ability to understand speech, and is widely believed to be associated with cochlear amplification. However, genetic studies targeting the tectorial membrane (TM) have demonstrated both sharper and broader tuning with no obvious changes in hair bundle or somatic motility mechanisms. For example, cochlear tuning of Tectb(-/-) mice is significantly sharper than that of Tecta(Y1870C/+) mice, even though TM stiffnesses are similarly reduced relative to wild-type TMs. Here we show that differences in TM viscosity can account for these differences in tuning. In the basal cochlear turn, nanoscale pores of Tecta(Y1870C/+) TMs are significantly larger than those of Tectb(-/-) TMs. The larger pore size reduces shear viscosity (by ∼70%), thereby reducing traveling wave speed and increasing spread of excitation. These results demonstrate the previously unrecognized importance of TM porosity in cochlear and neural tuning.


Subject(s)
Tectorial Membrane/chemistry , Vibration , Animals , Extracellular Matrix Proteins/genetics , Extracellular Matrix Proteins/metabolism , GPI-Linked Proteins/genetics , GPI-Linked Proteins/metabolism , Mice , Mice, Inbred C57BL , Porosity , Tectorial Membrane/metabolism , Tectorial Membrane/physiology , Viscosity
4.
Proc Natl Acad Sci U S A ; 110(11): 4279-84, 2013 Mar 12.
Article in English | MEDLINE | ID: mdl-23440188

ABSTRACT

The tectorial membrane (TM) clearly plays a mechanical role in stimulating cochlear sensory receptors, but the presence of fixed charge in TM constituents suggests that electromechanical properties also may be important. Here, we measure the fixed charge density of the TM and show that this density of fixed charge is sufficient to affect mechanical properties and to generate electrokinetic motions. In particular, alternating currents applied to the middle and marginal zones of isolated TM segments evoke motions at audio frequencies (1-1,000 Hz). Electrically evoked motions are nanometer scaled (∼5-900 nm), decrease with increasing stimulus frequency, and scale linearly over a broad range of electric field amplitudes (0.05-20 kV/m). These findings show that the mammalian TM is highly charged and suggest the importance of a unique TM electrokinetic mechanism.


Subject(s)
Electrophysiological Phenomena/physiology , Mechanotransduction, Cellular/physiology , Tectorial Membrane/physiology , Animals , Kinetics , Male , Mice , Motion
5.
J Biomater Appl ; 21(3): 235-49, 2007 Jan.
Article in English | MEDLINE | ID: mdl-16543287

ABSTRACT

In this study, a method for the rapid generation of a variety of bifunctional surfaces that can serve to quickly determine the selective adhesion of HEK293 cells towards different chemical functionalities has been established. Using the information about selective adhesion of HEK293 cells to bifunctional surfaces, we demonstrate the ability to construct stable, high density, and multi-welled surfaces where the mammalian cells form the walls of picoliter volume wells.


Subject(s)
Cell Culture Techniques/instrumentation , Dimethylpolysiloxanes/chemistry , Kidney/cytology , Kidney/physiology , Nanostructures/chemistry , Nylons/chemistry , Cell Culture Techniques/methods , Cell Line , Cell Proliferation , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Equipment Design , Equipment Failure Analysis , Humans , Nanostructures/ultrastructure , Surface Properties
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