The objective of this application is to gain understanding of the roles of the various matrix constituents in the physiology and pathology of teeth and bones, with a view to eventual practical applications to health problems ranging from dental caries to bone fracture healing. The role of the organic structural framework (organic matrix) during mineralization of skeletal hard parts is not well understood. At the ultrastractural level many vertebrate mineralized tissues show an intimate relationship between the mineral crystals and the matrix, but the nature of the association at the molecular level is not clear, primarily because the conformations of almost all matrix macromolcules, except for collagen, are not known. A considerable number of noncollagenous proteins have been isolated from teeth and bones and, from various indications, several are implicated in mediating apatite crystal growth; some, including dentin phosphoryn and bone osteonectin, have been related to pathological conditions.
The aim of this proposal is to analyse the molecular conformations of matrix components in enamel, dentin and bone and to relate these to the associated mineral phase. Firstly, it is planned to study conformations and matrix-mineral relationships in situ using X-ray fiber diffraction, as well as electron diffraction and Fourier transform infrared spectroscopy. Secondly, it is intended to study the conformations of various isolated matrix proteins, including enamelin, amelogenin, phosphoryn and osteonectin, using X-ray diffraction and infrared spectroscopy. The proteins will be treated with various solvents and counterions and attempts made to prepare oriented fibers, as well as single crystals, which could be subjected to detailed structure analysis. Structure determination from single crystals of matrix proteins would be of great scientific interest as no detailed structure of a protein involved in biomineralization has yet been determined. This proposed study could serve to elucidate some of the fundamental mechanisms involved in crystal growth by animals.
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