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.

National Institute of Health (NIH)
National Institute of Dental & Craniofacial Research (NIDCR)
Research Project (R01)
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Biomaterials and Biointerfaces Study Section (BMBI)
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Wan, Jason
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University of Washington
Biomedical Engineering
Schools of Engineering
United States
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Roehrich, Adrienne; Drobny, Gary (2013) Solid-state NMR studies of biomineralization peptides and proteins. Acc Chem Res 46:2136-44
Weidner, Tobias; Castner, David G (2013) SFG analysis of surface bound proteins: a route towards structure determination. Phys Chem Chem Phys 15:12516-24
Breen, Nicholas F; Li, Kun; Olsen, Gregory L et al. (2011) Deuterium magic angle spinning NMR used to study the dynamics of peptides adsorbed onto polystyrene and functionalized polystyrene surfaces. J Phys Chem B 115:9452-60
Ndao, Moise; Ash, Jason T; Stayton, Patrick S et al. (2010) The Role of Basic Amino Acids in the Molecular Recognition of Hydroxyapatite by Statherin using Solid State NMR. Surf Sci 604:L39-L42
Weidner, Tobias; Breen, Nicholas F; Li, Kun et al. (2010) Sum frequency generation and solid-state NMR study of the structure, orientation, and dynamics of polystyrene-adsorbed peptides. Proc Natl Acad Sci U S A 107:13288-93
Masica, David L; Ash, Jason T; Ndao, Moise et al. (2010) Toward a structure determination method for biomineral-associated protein using combined solid- state NMR and computational structure prediction. Structure 18:1678-87
Ndao, Moise; Ash, Jason T; Breen, Nicholas F et al. (2009) A (13)C{(31)P} REDOR NMR investigation of the role of glutamic acid residues in statherin- hydroxyapatite recognition. Langmuir 25:12136-43
Breen, Nicholas F; Weidner, Tobias; Li, Kun et al. (2009) A solid-state deuterium NMR and sum-frequency generation study of the side-chain dynamics of peptides adsorbed onto surfaces. J Am Chem Soc 131:14148-9
Goobes, Gil; Stayton, Patrick S; Drobny, Gary P (2007) Solid State NMR Studies of Molecular Recognition at Protein-Mineral Interfaces. Prog Nucl Magn Reson Spectrosc 50:71-85
Goobes, Rivka; Goobes, Gil; Shaw, Wendy J et al. (2007) Thermodynamic roles of basic amino acids in statherin recognition of hydroxyapatite. Biochemistry 46:4725-33

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