Visualizable regulation of brushite mineralization by carboxylated gold nanoclusters: From liquid precursor formation to crystal growth.

Acidic carboxylated biomolecules play a pivotal role in regulating the nucleation and growth of inorganic crystals during biomineralization, yet their dynamic behavior throughout the crystallization process remains elusive due to technical limitations in tracking. Herein, we report a biomimetic strategy using carboxylated gold nanoclusters (Au NCs) as carboxylated biomolecules mimics, leveraging their high electron density and fluorescence to visualize brushite (dicalcium phosphate dihydrate, DCPD) mineralization under acidic conditions. Rod-shaped DCPD forms at pH 5.0, while plate-like DCPD is observed at pH 6.5. The carboxyl groups of Au NCs bind to Ca2+ ions, inducing the aggregation of calcium phosphate liquid-like precursor and their subsequent transformation into DCPD. High-resolution transmission electron microscopy (HRTEM) reveals that Au NCs are uniformly dispersed in the initial liquid-like precursor and gradually excluded to the crystal edges during crystallization. Fluorescence microscopy further confirms the localization of Au NCs along the DCPD crystal edges. This work elucidates the mechanism by which carboxylated Au NCs modulate DCPD crystal growth and provides a promising visualizable tool for probing calcium phosphate crystallization pathways. Moreover, it expands the design of biomimetic mineralization regulators and offers valuable insights for fundamental research on crystal growth control.