The role of prenucleation clusters in surface-induced calcium phosphate crystallization

Unravelling the processes of calcium phosphate formation(1-4) is important in our understanding of both bone and tooth formation(5-7), and also of pathological mineralization, for example in cardiovascular disease(8-10). Serum is a metastable solution from which calcium phosphate precipitates in the presence of calcifiable templates such as collagen, elastin and cell debris(11,12). A pathological deficiency of inhibitors leads to the uncontrolled deposition of calcium phosphate. In bone and teeth the formation of apatite crystals is preceded by an amorphous calcium phosphate (ACP) precursor phase(13,14). ACP formation is thought to proceed through prenucleation clusters-stable clusters that are present in solution already before nucleation-as was recently demonstrated for CaCO3 (refs 15,16). However, the role of such nanometre-sized clusters as building blocks(2) for ACP has been debated for many years. Here we demonstrate that the surface-induced formation of apatite from simulated body fluid(17,18) starts with the aggregation of prenucleation clusters leading to the nucleation of ACP before the development of oriented apatite crystals.