Biomineralization from the Perspective of Ion Aggregation: Calcium Phosphate Nucleation in the Physiological Environment

Biomineralization is an important process of bone tissue generation. Calcium (Ca) and phosphate (P) ions aggregate and nucleate under the regulation of biomolecules at the initial mineralization stage. Due to the complexity of the physiological environment, the movement behavior and mineralization mechanism of calcium and phosphate ions, as well as the effect of biomolecules on them, are not clear. In this study, computer simulations and experimental verification were applied to investigate the characteristics of the initial biomineralization from the view of ion aggregation and nucleation. The results prove that P ions play a more important role in mineralization than Ca ions. The guanidyl group and surrounding carboxyl terminal groups are a potential excellent nucleation domain on proteins. The interval distribution of acidic/basic residues on protein is more conductive to the formation of large Ca and P ions clusters. The involvement of protein could increase the probability of hydroxyapatite phase precipitation, especially in the presence of a helical conformation. The detailed information on Ca and P ions behavior provided by the computer simulations is helpful for further understanding the mechanism of biomineralization, which will promote the development of bone repair materials to the biomimetic mineralized materials.