Biomechanics of Vertebrate Hair Cells

脊椎动物毛细胞的生物力学

• 批准号: 6369651
• 负责人: ELLENGENE H PETERSON
• 金额: $ 49.23万
• 依托单位: OHIO UNIVERSITY ATHENS
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-07-01 至 2006-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6369651
• 关键词: Chelonia; Chordata; biological signal transduction; biomechanics; cell cell interaction; cell component structure /function; cell population study; cilium; computer simulation; confocal scanning microscopy; ear hair cell; elasticity; electron microscopy; electrophysiology; epithelium; head movements; immunocytochemistry; labyrinth; light microscopy; model design /development; morphology; morphometry; neural transmission; physical model; sensorimotor system; voltage /patch clamp

Hair dells are the receptors that vertebrates us to detect sound, head movement, vibrations, and gravity. Each of these sensations begins with a mechanical stimulus. Hair cells respond to this stimulus via a complex cellular process that shapes the primary afferent signal to the central nervous system. The first step in this process and the one on which all others depend is deflect of the hair cell's ciliary bundle. Unfortunately, the mechanical and cellular mechanisms that govern this first critical step are poorly understood. The long term goal of the proposed research is to understand these fundamental mechanisms of mechanotransduction by hair cells and to develop a realistic computational model of this process. It is a collaborative bioengineering effort that uses state-of-the-art imaging and computational technology. The proposed research has three bioengineering effort that uses state-of-the-art imaging and computational technology. The proposed research has three Specific Aims. (1) We will use light and electron microscopic techniques to characterize quantitatively the structure of hair cells, emphasizing those features of their ciliary bundles that are likely to affect the hair ells' mechanical performance, and we will use brightfield and confocal microscopy to visualize the coupling between hair bundles and the overlying otolithic membranes in living utricles. (2) We will incorporate these data into a structurally accurate finite element model of the ciliary bundle that will quantify the contribution of different structural elements (e.g., number, height, and interconnections of stereocilia) and the in vivo stimulus to the static stiffness and response dynamics of morphologically distinct varieties of hair cells. Then we will test and refine our model predictions by experimental tests on living bundles. (3) We will use our computational model to predict current-displacement relations in bundles of different types. Then we will use whole-cell patch clamp recording from living hair cells to further test and refine our model predictions. These studies will provide, important information about mechanisms of mechanotransduction and the functional significance of ciliary bundle structure. The resulting computational model will be a powerful resource in future attempts to understand the mechanical performance of any vertebrate hair cells.

戴毛发丝是脊椎的受体，可以检测声音，头部运动，振动和重力。这些感觉中的每一个都始于机械刺激。毛细胞通过复杂的细胞过程对这种刺激做出反应，该过程塑造了中枢神经系统的主要传入信号。此过程的第一步，所有其他过程都依赖于毛细胞的睫状束的偏转。不幸的是，对第一个关键步骤的控制的机械和细胞机制知之甚少。拟议的研究的长期目标是了解毛细胞的机械转导的这些基本机制，并开发此过程的现实计算模型。这是一种使用最先进的成像和计算技术的协作生物工程工作。拟议的研究有三项生物工程工作，使用最先进的成像和计算技术。拟议的研究具有三个具体目标。 （1）我们将使用光和电子显微镜技术来定量表征毛细胞的结构，强调其睫状捆的那些特征，这些特征可能会影响头发ELL的机械性能，并且我们将使用Brightfield和Condocal显微镜来可视化头发束中的搭配和覆盖层的Otololith otololithic embranes in Lived Utrycrane embranes in Live Utrycranes中。 （2）我们将将这些数据纳入睫状束的结构准确的有限元模型中，该模型将量化不同结构元素（例如，数量，高度和立体胶体的互连）和体内刺激对静态刚度的贡献（例如数量，高度和互连），并具有膜细胞形态上不同品种的静态刚度和响应动力学。然后，我们将通过对活捆的实验测试进行测试和完善模型预测。 （3）我们将使用我们的计算模型来预测不同类型的束中的电流置换关系。然后，我们将使用从活毛细胞的全细胞贴片夹记录来进一步测试和完善我们的模型预测。这些研究将提供有关机械转移机制的重要信息以及睫状束结构的功能意义。最终的计算模型将是未来尝试了解任何脊椎动物毛细胞机械性能的强大资源。