The interactions of proteins with material surfaces is a fundamental aspect of biomedical technology, but little is known of the molecular-level mechanisms underlying the binding of proteins to biomineral surfaces. Even less is known of how proteins structurally adapt to non-native material surfaces.
The aim of this R21 proposal is to apply a solid state NMR approach to elucidating the fundamental molecular-level nature of interactions between extracellular matrix (ECM) proteins, that have evolved to interact with biological materials like hydroxyapatite (Hap), and inorganic oxides that are used as coatings for dental implants and scaffolds. Salivary statherin is an enamel pellicle protein that inhibits hydroxyapatite (Hap) nucleation and growth, and is an adhesion site for oral bacteria involved in periodontal disease. Statherin is one of the few biomineralization proteins for which there is an experimentally constrained structure of the surface-bound form. In this project statherin will be used as a model to study how ECM proteins adapt structurally to implant material interfaces. We will focus on statherin?s structure/interactions with titanium (IV) oxide TiO2 , whose properties as an implant coating have been studied extensively. The anticipated outcome of this two year research effort is the development of a solid state NMR-based methodology which provides a rational, structure-based approach for predicting protein binding to and folding on inorganic oxide surfaces and other materials used as dental implant materials..
When a medical or dental implant is placed in contact with living tissue, interactions between the implant surface and the cell are mediated by a proteinaceous layer, which ideally promotes cell adhesion to the implant surface and normal cellular response. Non-specific adsorption of proteins or the presence of proteins in an unstructured or otherwise unrecognized state may result in a foreign body response and implant failure. This exploratory research program aims to use solid state NMR to study the nature of interactions between proteins and implant materials, focusing at first on titanium (IV) oxide, with the ultimate objective of obtaining a molecular-level structure-based approach to optimizing implant materials for interactions with proteins.