The remarkable material properties of bone and teeth arise because of the sophisticated crystal engineering capabilities of proteins, and the long-term objective of our research is to elucidate the molecular recognition mechanisms used by proteins to control biomineralization processes. The activities of proteins at the organic-inorganic interface are critical to the maintenance of hard tissue function. The disruption of these processes has profound medical and dental ramifications, leading for example to bone and tooth demineralization, atherosclerotic plaque formation, artificial heart valve calcification, kidney and gall stone build-up, and dental calculus formation. It is widely recognized that the molecular details of protein function at the organic-inorganic interface are just beginning to emerge. This research program has been developing and applying solid- state NMR (ssNMR) techniques to determine protein structure and dynamics on their biologically relevant hydroxyapatite surface, together with the inter-related thermodynamic and kinetic characterization of hydroxyapatite recognition and crystal growth dynamics. These studies have led to the beginnings of a high-resolution model for the acidic salivary protein statherin that connects structure to function. The goal in the continuation period is to test and develop a full three-dimensional statherin structure that connects to the molecular mechanisms underlying hydroxyapatite adsorption thermodynamics and crystal engineering function. The significance of pushing this frontier forward will be found in the development of calcification inhibitors and promoters that could impact the dental field, as well as orthopedics, urology, and the cardio- vascular fields. A better understanding of how these proteins recognize and assemble in bioactive fashion on inorganic mineral phases could aid in the development of surface coatings to improve the biocompatibility of implantable biomaterials and tissue engineering scaffolds. This project aims to develop a molecular understanding of how salivary proteins control the growth of hydroxyapatite, the mineral phase of teeth. Information from these studies could be used to design biomimetic peptide coatings for biomaterial/tissue engineering applications, and could provide new routes to inhibiting the bacterial adhesion steps that underlie dental caries (e.g. gingivitis) development.
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