Role of Metabolic Acids in Shaping Bone-like Apatite Architectures

Bone mineral forms both inside and between collagen fibrils in the extracellular matrix. While the morphology of intrafibrillar bone mineral has been hypothesized to be primarily controlled by the size and shape of the restricted spaces inside collagen fibrils within which the mineral forms, what controls the architecture of the extrafibrillar mineral is still an open question. While bone mineral is primarily apatitic in composition, it also contains significant quantities of cell respiration metabolites, in particular, carbonate, citrate, and lactate. An as-yet unanswered question is what, if any, role do these metabolites collectively play in determining the 3D architecture of bone mineral. Here, we propose a composite model of bone mineral that accounts for both intra- and extrafibrillar mineral environments, and to that end, we develop apatitic materials containing citrate and lactate or carbonate that mimic the densely packed ionic environments within which bone mineral forms in vivo. We find that incorporating citrate and lactate leads to complex mineral architectures reminiscent of those in extrafibrillar bone mineral, including mineral crystal curvature. Our results suggest that metabolic acids may play an important role in building the 3D architecture of extrafibrillar bone mineral.