Principal Investigator: VLADIMIR L TSUPRUN
Abstract: DESCRIPTION (from applicant's abstract): The extracellular matrix, one of the basic constituents of the cochlea, encompasses all of the connective tissue structures of the cochlea (tectorial membrane, spiral limbus, basilar membrane, spiral ligament, and extracellular stereocilia links). The extracellular matrix plays an important structural and mechanical role and is involved in transduction of sound-induced mechanical stimuli into electrical signals. Structural abnormalities of the matrix may lead to different types of hearing disorders. However, molecular composition and structure of this matrix are not well understood. The overall goal of this project is to test the hypothesis that the extracellular matrix in the cochlea consists of symmetric macromolecular arrays, which determine its properties and provide integrity to the cochlear matrix and cells. The project includes two specific aims: 1. To determine the ultrastructure of the cochlear extracellular matrix. The structure of regularly distributed fibronectin fibrils in the basilar membrane and their association with collagen, tenascin, and other molecules will be studied. Knowledge of the supramolecular organization of collagen, fibronectin, tenascin, and other molecules may provide a foundation upon which micromechanical models of the cochlea can be constructed. We will focus also on the ultrastructure of proteoglycans arrays in different types of cochlear basement membranes (subepithelial, endothelial, perineural) related to their location, diverse properties and functions. 2. To determine the structure of the outer hair cell stereocilia links. The structure of periodically arranged side links, rotationally distributed 'attachment links,' and helical organization of the tip links will be investigated to find a relationship between the structure and role of these symmetric arrays. The tip links play an important role in mechano-electrical transduction of the sound waves, and a substantial part of this application includes the study of its helical structure, found recently in these links. These aims will use transmission electron microscopy of thin cochlear sections, in which the molecular structures have been preserved and stained at a resolution sufficient for their computer image analysis. Methods of structural crystallography, Fourier (Fast Fourier Transformation) image analysis of periodic objects, and computer averaging to obtain enhanced, noise-free images will be applied in this study.
Funding Period: 2001-01-01 - 2003-12-31
more information: NIH RePORT