Amino Acid/Ion Aggregate Formation and Their Role in Hydroxyapatite Precipitation

Hydroxyapatite (HA, Ca₅(PO₄)₃OH) constitutes the inorganic component of bone. Its formation is regulated by noncollagenous proteins and especially negatively charged amino acids present in their structure. Here we show that Ca²⁺ and PO₄^3– ions can interact with both a negative (Glu) and a positive (Arg) amino acid, and form aggregates that grow if left undisturbed. Depending on how long these aggregates are allowed to grow, once they come into contact they give rise to HA crystals that form at different times and that differ in content and properties. This finding points out that the aging time of precursor solutions is an important variable that needs to be taken into account in all biomineralization experiments and that not only proteins but also small molecules like amino acids can form aggregates that alter biomineral formation. The formation of biomolecular aggregates in the aged precursor solutions may also mirror what happens in vivo, where biominerals are formed upon compartmentalization of precursor ions and mineralization inhibitors or promoters