MECHANICS OF THE COCHLEAR OUTER HAIR CELL

耳蜗外毛细胞的力学

• 批准号: 6175366
• 负责人: WILLIAM E BROWNELL
• 金额: $ 37.2万
• 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/6175366
• 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机理。 并确定特定细胞器的贡献 (下池、皮质格子和细胞膜) 侧壁)和细胞质与细胞的机械性能有关。 这一知识对于理解OHC在 耳蜗力学，特别是被动机械和主动机械 过滤。该项目的一个具体目标是描述OHC轴的特征 力-位移函数；此函数对于计算 外毛细胞对周围环境施加的力的大小 结构作为OHC电动的结果。协同实验 而理论研究将指向研究弹性 和细胞的粘弹性特性。高分辨率视频显微镜 将被用来记录分离的豚鼠内皮细胞对 通过贴片吸管吸入微管和细胞充气，并 观察细胞质中的珠子在热驱动下的运动。位移 从每个刺激将从视频的延时分析中测量 图像。这方面的研究主要集中在横向的细观力学上。 墙。将应用各种药物治疗来修改 构成侧壁的亚细胞成分。机械的 未处理的OHC的特性将与那些 经过药物处理的细胞。OHC的理论模型作为一种 两端有盖的充液粘弹性圆柱壳 将被开发来分析实验结果。该模型将 将电池的径向刚度与其压力-充气响应联系起来 到轴向力-位移函数。理论分析将会 也可用于分析动态的直接测量结果 孤立单元轴向加载过程中的力-位移函数。这个 计算结果将给出静力和静力作用下的轴向力-位移函数。 动态条件，并允许精确确定OHC驾驶 对耳蜗力学的作用力，这将有助于描绘机械 OHC对被动和主动机械过滤的贡献。 这些研究的结果将量化OHC在 细胞和亚细胞水平，并作为研究的基础 OHC电动的分子机制。了解以下内容 微结构元素及其在OHC力学中的功能意义 将加深我们对OHC如何对哺乳动物的贡献的理解 健康和疾病方面的听证。