Monomeric Amelogenin’s C-Terminus Modulates Biomineralization Dynamics of Calcium Phosphate

The organic matrix in forming enamel consists largely of the self-assembled nanospheres of amelogenin monomers that play a critical role in controlling crystal growth of the highly organized apatites. However, little is known about the mechanisms of the monomeric form of the C-terminal tail of the molecule in regulating biomineralization dynamics. We investigated brushite–amelogenin’s C-terminus interactions by in situ atomic force microscopy (AFM). At very low concentrations (1–10 nM) within a monomeric form of amelogenin, we directly observe a strong interaction of monomeric amelogenin’s C-terminus binding to the brushite (010) face, which modulates the critical length and terrace width of moving steps through modification of the brushite–water interfacial energies. This in turn inhibits crystallization by delaying the formation of active steps on the growing crystal face. These findings provide the underlying thermodynamics for understanding biomineral formation, reflecting monomeric protein interactions with precursor phases of developing enamel crystals.