Biomechanics of Vertebrate Hair Cells

脊椎动物毛细胞的生物力学

• 批准号: 6634557
• 负责人: ELLENGENE H PETERSON
• 金额: $ 42.7万
• 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/6634557
• 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.

毛谷是脊椎动物感知声音、头部运动、振动和重力的感受器。这些感觉中的每一种都始于机械刺激。毛细胞通过复杂的细胞过程对这种刺激做出反应，该过程形成中枢神经系统的主要传入信号。这个过程的第一步，也是所有其他过程所依赖的一步，是毛细胞睫状束的偏转。不幸的是，人们对控制这第一个关键步骤的机械和细胞机制知之甚少。拟议研究的长期目标是了解毛细胞机械传导的这些基本机制，并开发该过程的现实计算模型。这是一项协作生物工程工作，使用最先进的成像和计算技术。拟议的研究涉及三项生物工程工作，使用最先进的成像和计算技术。拟议的研究有三个具体目标。 (1) 我们将使用光学和电子显微镜技术来定量表征毛细胞的结构，强调可能影响毛细胞机械性能的纤毛束的那些特征，并且我们将使用明场和共聚焦显微镜来可视化活体椭圆囊中毛束和上覆耳石膜之间的耦合。 (2) 我们将把这些数据纳入结构精确的纤毛束有限元模型中，该模型将量化不同结构元素（例如静纤毛的数量、高度和互连）的贡献以及对形态不同的毛细胞品种的静态刚度和响应动力学的体内刺激。然后我们将通过对活束进行实验测试来测试和完善我们的模型预测。 (3) 我们将使用我们的计算模型来预测不同类型束中的电流-位移关系。然后我们将使用活毛细胞的全细胞膜片钳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力传导机制和睫状束结构功能意义的重要信息。由此产生的计算模型将成为未来了解任何脊椎动物毛细胞机械性能的强大资源。