This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The non-collagenous proteins and proteoglycans in bone tissue comprise about 1% by weight of the material, but are known to provide a number of vital functions, including controlling spatial orientation of mineral crystal lites and regulating mineral growth. More recently they have been proposed to playa structural role in mature bone tissue as well. However, identifying key noncollagenous matrix components and their roles in the growth and architecture of bone tissue has proven a significant challenge due to the small relative amounts of these components. Mineral growth in bone is strictly regulated by elements of the surrounding organic matrix to restrict crystal size and control crystal orientation in order to achieve optimal mechanical properties for its function. Mineral crystals are grown with a specific orientation relative to the collagen fibers in the tissue, leading to the mechanical anisotropy that is characteristic of bone tissue. The matrix proteins that regulate and direct crystal growth, and their interactions with collagen and bone mineral, are not well understood. A structural role for non-collagenous matrix components in bone has recently come to light through the work of Paul Hansma and colleagues. They have measured the mechanical effects of an as-yet-unidentified matrix component they term """"""""molecular glue"""""""" on the toughness of bone tissue. The existence of this """"""""glue"""""""" has implications in fragile-bone diseases, most notably osteoporosis, in which an absence or loss of function of this matrix component could compromise the mechanical function of the tissue. The identities and interactions of the non-collagenous matrix components playing these important structural roles in bone are not yet understood;much work remains in order to understand this complex tissue and the changes in it that occur in a disease state.
The aim of the proposed work is to identify non-collagenous protein candidates for each of the roles described above. Candidates will be screened for interaction with collagen and hydroxyapatite mineral using fluorescence binding, electrophoresis, and NMR relaxation techniques. To elucidate specific models of interaction between these proteins and the collagen/mineral components of bone, synthetic peptides of non-collagenous protein domains will be synthesized and their interactions with collagen and hydroxyapatite mineral investigated using fluorescence resonance energy transfer (FRET) and solid-state NMR techniques.
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