Three-dimensional and Multiscale Organ of Corti Biomechanics

点击翻译按钮获取中文摘要

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.