Accurate Force Field Parameters and pH Resolved Surface Models for Hydroxyapatite to Understand Structure, Mechanics, Hydration, and Biological Interfaces

Mineralization of bone and teeth involves interactions between biomolecules and hydroxyapatite. Associated complex interfaces and processes remain difficult to analyze at the 1 to 100 rim scale using current laboratory techniques, and prior apatite models for atomistic simulations have been limited in the representation of chemical bonding, surface chemistry, and interfacial interactions. In this contribution, an accurate force field along with pH-resolved surface models for hydroxyapatite is introduced to represent chemical bonding, structural, surface, interfacial, and mechanical properties in quantitative agreement with experiment. The accuracy is orders of magnitude ligher in comparison to earlier models and facilitates quantitative monitoring of inorganic-biological assembly. The force field is integrated into the AMBER, CHARMM, CFF, CVFF, DREIDING, GROMACS, INTERFACE, OPLS-AA, and PCFF force fields to enable realistic simulations of apatite-biological systems of any composition and ionic strength. Specific properties that are reproduced well in comparison to experiment include lattice constants (<0.5% deviation), IR spectrum, cleavage energies, immersion energies in water (<5% deviation), and elastic constants (<10% deviation). Interactions between mineral, water, and organic compounds are represented by standard combination rules without additional adjustable parameters and shown to achieve quantitative precision. Surface models for common (001), (010), (020), and (101) facets and nanocrystals are introduced as a function of pH on the basis of extensive experimental data. New insights into surface and immersion energies, the structure of aqueous interfaces, density profiles, and superficial dissolution are described. Most notably, hydroxyapatite-water interfaces exhibit facet-specific and pH-specific density profiles. Water stabilizes (010) facets better than (001) facets in a pH range from 10 to 5, consistent with preferred nanocrystal shape and growth in the (001) direction observed in experiment. Towards lower pH values, increasing penetration of water into sub-surface layers is observed, water density profiles flatten, and superficial dissolution occurs. The force field and surface models can be applied to elucidate mechanisms of mineralization as well as specific binding and assembly of peptides, polymer, and drugs. Extensions to substituted and defective apatites as well as to other calcium phosphate phases are feasible.