Modeling the Mechanics of Tethers Pulled From the Cochlear Outer Hair Cell Membrane

Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21205, USA.
Journal of Biomechanical Engineering (Impact Factor: 1.78). 07/2008; 130(3):031007. DOI: 10.1115/1.2907758
Source: PubMed


Cell membrane tethers are formed naturally (e.g., in leukocyte rolling) and experimentally to probe membrane properties. In cochlear outer hair cells, the plasma membrane is part of the trilayer lateral wall, where the membrane is attached to the cytoskeleton by a system of radial pillars. The mechanics of these cells is important to the sound amplification and frequency selectivity of the ear. We present a modeling study to simulate the membrane deflection, bending, and interaction with the cytoskeleton in the outer hair cell tether pulling experiment. In our analysis, three regions of the membrane are considered: the body of a cylindrical tether, the area where the membrane is attached and interacts with the cytoskeleton, and the transition region between the two. By using a computational method, we found the shape of the membrane in all three regions over a range of tether lengths and forces observed in experiments. We also analyze the effects of biophysical properties of the membrane, including the bending modulus and the forces of the membrane adhesion to the cytoskeleton. The model's results provide a better understanding of the mechanics of tethers pulled from cell membranes.

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Available from: Aleksander S Popel
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    • "Accurate characterization of the mechanical properties of individual cells within the organ of Corti should thus help in the construction of more accurate models of cochlear mechanics [1]. Whilst attention has been given to the mechanical properties of hair cells [8], [9], [10], [11], [12], [13], [14], [15], [16] and their mechanosensory bundles [17], [18], a systematic analysis of supporting cells has not been undertaken. "
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    ABSTRACT: The mechanical properties of the mammalian organ of Corti determine its sensitivity to sound frequency and intensity, and the structure of supporting cells changes progressively with frequency along the cochlea. From the apex (low frequency) to the base (high frequency) of the guinea pig cochlea inner pillar cells decrease in length incrementally from 75-55 µm whilst the number of axial microtubules increases from 1,300-2,100. The respective values for outer pillar cells are 120-65 µm and 1,500-3,000. This correlates with a progressive decrease in the length of the outer hair cells from >100 µm to 20 µm. Deiters'cell bodies vary from 60-50 µm long with relatively little change in microtubule number. Their phalangeal processes reflect the lengths of outer hair cells but their microtubule numbers do not change systematically. Correlations between cell length, microtubule number and cochlear location are poor below 1 kHz. Cell stiffness was estimated from direct mechanical measurements made previously from isolated inner and outer pillar cells. We estimate that between 200 Hz and 20 kHz axial stiffness, bending stiffness and buckling limits increase, respectively,∼3, 6 and 4 fold for outer pillar cells, ∼2, 3 and 2.5 fold for inner pillar cells and ∼7, 20 and 24 fold for the phalangeal processes of Deiters'cells. There was little change in the Deiters'cell bodies for any parameter. Compensating for effective cell length the pillar cells are likely to be considerably stiffer than Deiters'cells with buckling limits 10-40 times greater. These data show a clear relationship between cell mechanics and frequency. However, measurements from single cells alone are insufficient and they must be combined with more accurate details of how the multicellular architecture influences the mechanical properties of the whole organ.
    Preview · Article · Nov 2012 · PLoS ONE
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    ABSTRACT: Membrane tethers can form naturally such as during leukocyte rolling (pre-adhesion) stage. Tethers can also be experimentally pulled from cellular membranes to estimate membrane mechanical and electromechanical properties, including bending modulus, adhesion energy of the membrane-cytoskeleton interaction, tension, and electromechanical forces produced by membranes. This technique has been effectively applied to a variety of cells such as red blood cells [1], neutrophils [2], and cochlear outer hair cells [3,4]. Fig. 1 presents the experiment where tethers are pulled from cellular membranes using optically trapped beads.
    No preview · Conference Paper · Jun 2009
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    ABSTRACT: Tethers are thin membrane tubes that can be formed when relatively small and localized forces are applied to cellular membranes and lipid bilayers. Tether pulling experiments have been used to better understand the fine membrane properties. These include the interaction between the plasma membrane and the underlying cytoskeleton, which is an important factor affecting membrane mechanics. We use a computational method aimed at the interpretation and design of tether pulling experiments in cells with a strong membrane-cytoskeleton attachment. In our model, we take into account the detailed information in the topology of bonds connecting the plasma membrane and the cytoskeleton. We compute the force-dependent piecewise membrane deflection and bending as well as modes of stored energy in three major regions of the system: body of the tether, membrane-cytoskeleton attachment zone, and the transition zone between the two. We apply our method to three cells: cochlear outer hair cells (OHCs), human embryonic kidney (HEK) cells, and Chinese hamster ovary (CHO) cells. OHCs have a special system of pillars connecting the membrane and the cytoskeleton, and HEK and CHO cells have the membrane-cytoskeleton adhesion arrangement via bonds (e.g., PIP2), which is common to many other cells. We also present a validation of our model by using experimental data on CHO and HEK cells. The proposed method can be an effective tool in the analyses of experiments to probe the properties of cellular membranes.
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