MECHANICS OF THE COCHLEAR OUTER HAIR CELL

耳蜗外毛细胞的力学

• 批准号: 2414665
• 负责人: WILLIAM E BROWNELL
• 金额: $ 38.32万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-05-01 至 2001-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2414665
• 关键词: actins; biomechanics; cell wall; cytochalasins; cytoplasm; ear hair cell; ear pharmacology; elasticity; guinea pigs; mathematical model; model design /development; salicylate; trypsin; video microscopy; viscosity

The goal of this research is to investigate the mechanics of outer hair cell (OHCs) and to determine the contribution of specific organelles (subsurface cisterna, cortical lattice and cytoplasmic membrane of the lateral wall) and the cytoplasm to the mechanical properties of the cell. This knowledge is necessary for understanding the role of the OHC in cochlear mechanics, specifically in passive and active mechanical filtering. A specific goal of the project is to characterize the OHC axial force-displacement function; this function is crucial for evaluating the magnitude of the forces that outer hair cells exert on the surrounding structures as the result of OHC electromotility. Coordinated experimental and theoretical studies will be directed towards investigating the elastic and viscoelastic properties of the cell. High resolution video microscopy will be used to record the response of isolated guinea pig OHCs to micropipet aspiration and cell inflation through a patch pipet, and to observe thermally driven movement of beads in the cytoplasm. Displacements from each stimulus will be measured from time-lapse analysis of video images. Much of this research focuses on the micromechanics of the lateral wall. A variety of pharmacological treatments will be applied to modify the subcellular components that make up the lateral wall. The mechanical properties of untreated OHCs will be compared with those of pharmacologically treated cells. A theoretical model of the OHC as a fluid-filled viscoelastic cylindrical shell that is capped at both ends will be developed to analyze the experimental results. The model will relate the radial stiffness of the cell and its pressure-inflation response to the axial force-displacement function. The theoretical analysis will also be applied to analyze the results of direct measurements of dynamic force-displacement function during axial loading of isolated cells. The results will provide the axial force-displacement function under static and dynamic conditions and permit a precise determination of the OHC driving force on cochlear mechanics, which will help delineate the mechanical contribution of the OHC to both passive and active mechanical filtering. The results of these studies will quantify the mechanics of the OHC at the cellular and subcellular level and serve as a basis for research on the molecular mechanisms of OHC electromotility. Knowledge of the microstructural elements and their functional significance in OHC mechanics will enhance our understanding of how the OHC contributes to mammalian hearing in health and disease.

这项研究的目的是研究外毛的力学原理 细胞 (OHC) 并确定特定细胞器的贡献 （地下池、皮质格子和细胞质膜 侧壁）和细胞质对细胞的机械性能的影响。 这些知识对于理解 OHC 在以下方面的作用是必要的： 耳蜗力学，特别是被动和主动机械 过滤。 该项目的一个具体目标是表征 OHC 轴 力-位移函数；该函数对于评估 外毛细胞对周围毛细胞施加的力的大小 结构作为 OHC 电动性的结果。 协调实验 理论研究将致力于研究弹性 和细胞的粘弹性。 高分辨率视频显微镜 将用于记录分离的豚鼠 OHC 对 通过贴片吸管进行微量吸液抽吸和细胞充气，并 观察细胞质中珠子的热驱动运动。 位移 每个刺激都将通过视频的延时分析来测量 图像。 这项研究的大部分集中在横向的微观力学上 墙。 将应用多种药物治疗来改变 构成侧壁的亚细胞成分。 机械 未经处理的 OHC 的特性将与未经处理的 OHC 的特性进行比较 经过药物处理的细胞。 OHC 的理论模型 两端封盖的充满流体的粘弹性圆柱壳 将开发用于分析实验结果。 该模型将 将单元的径向刚度与其压力-膨胀响应联系起来 为轴向力-位移函数。 理论分析将 也可用于分析动态直接测量的结果 孤立细胞轴向加载期间的力-位移函数。 这 结果将提供静态和静态下的轴向力-位移函数 动态条件并允许精确确定 OHC 驾驶 耳蜗力学上的力，这将有助于描述机械 OHC 对无源和有源机械滤波的贡献。 这些研究的结果将量化 OHC 的机制 细胞和亚细胞水平，并作为研究的基础 OHC 电动性的分子机制。 的知识 微观结构元素及其在 OHC 力学中的功能意义 将增强我们对 OHC 如何为哺乳动物做出贡献的理解 健康和疾病中的听力。