UC San Diego

Hydroxyapatite (HAP) is the predominant inorganic constituent of biological hard tissues. The physical and chemical properties of HAP are associated with its size, morphology, crystallinity and interfacial atomic structure. Although the crystal structure of HAP has been investigated in numerous studies, the chemical environment of its different crystal planes, especially its surface dependent interaction with biomolecules at an atomic level remains less understood. Since the surface only accounts for a small portion of the bulk crystal, distinguishing the surface from the overall structure remains challenging to assess experimentally. Solid-state nuclear magnetic resonance (ssNMR) has proven to be a powerful technique for resolving the bulk form the surface providing structural details at atomic resolution. In the present thesis, HAP nanoparticles (NPs) with varying crystallinities and distinct morphologies, including nanowire with a preferred growth orientation along the c axis, nanosheets that are dominant along a and b axes, nanorods that exhibit a hybrid phases, and amorphous HAP NPs have been synthesized and characterized. The structure, especially the surface of these HAP NPs, has been analyzed from the perspectives of the major constituents that are active in NMR, including 1H, 31P (Chapter 2) and 43Ca (Chapter 4). In Chapter 3, the chemical environments of the surfaces of these HAP NPs were further examined using aspartic acid (Asp) as an adsorption agent. Asp is a major component in dentin matrix protein and plays a crucial role mediating the deposition of rod-like HAP in teeth. The structural conformation and the dynamics of Asp molecules that interface with HAP have been investigated with a series of high resolution ssNMR techniques supported by molecular dynamic (MD) simulation. The binding configurations of Asp on HAP with different lattice planes were experimentally determined though rotational echo double resonance (REDOR) ssNMR distance measurements following further refinement by MD modeling. The last goal of this thesis is to provide insights into the process of biomineralization as discussed in Chapter 5. The formation of biological HAP is a process facilitated by various functional proteins, especially those containing domains rich in acidic residues, including poly-(Glu) and poly-(Asp-Ser-Ser) peptide, which are inspired by bone sialoprotein and dentin matrix protein, respectively. These peptides were synthesized in the lab and introduced into synthetic protocols to control the size and morphology of HAP NPs. The templating effect of the bio-inspired acidic agents and peptides were compared and discussed in detail.