Three-dimensional and Multiscale Organ of Corti Biomechanics

描述（由申请人提供）：我们的长期目标是了解支持正常听力的高灵敏度、高频率分辨率和非线性特性的耳蜗机制，这将允许对各种耳蜗病理、当前干预或未来干预（如耳蜗子结构再生）引起的这些结构变化进行功能表征。我们的方法是开发基于物理的，三维的，动态的计算模型，将新的和现有的信息耳蜗结构和性能，尺寸和几何结构的Corti器官和周围的细胞和流体环境的特点，以前没有实现的详细程度。渐近和数值方法将结合非常快速和有效的计算。几何形状和材料特性的大约80个参数将用于定义耳蜗结构的全面横截面，包括骨架和Reissner膜的毫米尺度、毛细胞索马的微米尺度和纤毛的尖端链接的纳米尺度。这种方法是必要的，以整合和理解越来越精确的显微解剖测量报告的几个实验室，包括我们的，以解释这些结构的动态生物力学相互作用，并解决现有的问题。在第一个目标中，将给出一个完整的模型考虑线性效应，包括行波和非线性效应的结合，包括合并的外毛细胞的电动性。第二个目标将是使用这种建模能力来研究来自骨传导信号的耳蜗响应。尽管骨传导刺激在几乎所有耳鼻喉科诊所都很重要，但目前还没有广泛接受的理论，根据现有理论难以解释最近的测量结果，并且以前没有建立基于物理的计算模型。因此，该提案的完成将形成核心基础，预计将从根本上改变我们对耳蜗功能，病理学和干预的理解。研究结果将适用于理解的生物力学效应的遗传操作的器官的Corti细胞结构和提高理解骨传导途径的耳蜗在高噪声环境中正常的听力保护是不够的。

DESCRIPTION (provided by applicant): Our long-term goal is to understand the cochlear mechanisms that support the high sensitivity, high frequency resolution, and non-linear properties of normal hearing, which will then allow functional characterization of changes to these structures arising from a variety of cochlear pathologies, or from current interventions, or from future interventions such as regeneration of cochlear sub structures. Our approach is to develop physically based, three-dimensional, dynamic computational models that incorporate new and existing information on cochlear structures and properties, dimensions and geometry of structures in the organ of Corti and characteristics of the surrounding cellular and fluid environment to a degree of detail not previously achieved. Asymptotic and numerical methods will be combined for very fast and efficient calculations. Some eighty parameters of geometry and material properties will be used to define a comprehensive cross section of the cochlear structures, including the millimeter scale of the bony shelf and Reissner's membrane, micrometer scale of hair cell soma, and the nanometer scale of the tip links of cilia. This approach is necessary to integrate and understand the increasingly precise microanatomy measures reported by several laboratories including ours, to explain the dynamic biomechanical interaction of these structures and to resolve existing questions. In the first aim, a full model consideration will be given to linear effects including the incorporation of traveling waves and non-linear effects, including incorporation of electromotility of the outer hair cells. The second aim will be to use this modeling capability to investigate cochlear responses from bone conduction signals. Despite the importance of bone conducted stimulation in nearly all otolaryngology clinics, no current theory is widely accepted, recent measurements are difficult to interpret in light of existing theory, and no physically-based computational model has previously been made. The completion of this proposal will therefore form the core foundation that is expected to fundamentally alter our understanding of cochlear function, pathology and intervention. The results will be applicable to understanding the biomechanical effects of genetic manipulations of the organ of Corti cytoarchitecture and improving understanding of bone-conduction pathways to the cochlea in high noise environments where normal hearing protection is inadequate.