The long term objective of this research is to elucidate the molecular recognition mechanisms used by proteins to control biomineralization processes, and to use this knowledge to design biomimetic peptide coatings for biomaterial/tissue engineering applications. Proteins found in mineralized tissues act as nature?s crystal engineers, where they play a key role in promoting or inhibiting the growth of minerals such as hydroxyapatite (bone/teeth) and calcium oxalate (kidney stones). Despite their importance in hard tissue formation and remodeling, and in pathological processes such as stone formation and arterial calcification, there is remarkably little known of the protein structure-function relationships that govern hard tissue engineering. Solid-state NMR (ssNMR) techniques are providing the first in situ secondary structure and dynamics determination of peptides/proteins on their biologically relevant hydroxyapatite surface. Combined with complementary physical-chemical and site-directed mutagenesis characterization of protein functional activities, these studies are beginning to yield truly molecular insight into the structure/function relationships controlling biomineral growth. In this research program, the structure, dynamics, and HAP recognition/engineering mechanisms utilized by two small salivary proteins that are amenable to detailed ssNMR and physical-chemical study will be investigated and contrasted. Statherin and histatin share some functional similarities, but are quite distinct in primary structure and electrostatic properties. Their comparison should thus provide interesting insight into the different routes biology has taken to achieve hydroxyapatite crystal engineering. This molecular insight has also led directly to the initial design of biomimetic fusion peptides that utilize nature?s crystal recognition mechanism to display accessible and dynamic bioactive sequences from the HAP surface. The fundamental studies will thus be connected to the design of bioactive peptides in the last aim.
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