The role of amino acids in hydroxyapatite mineralization

Abstract

Polar and charged amino acids (AAs) are heavily expressed in non-collagenous proteins (NCPs), and are involved in hydroxyapatite (HA) mineralization in bone. Here, we review what is known on the effect of single AAs on HA precipitation. Negatively charged AAs, such as aspartic acid, glutamic acid (Glu) and phosphoserine are largely expressed in NCPs and play a critical role in controlling HA nucleation and growth. Positively charged ones such as arginine (Arg) or lysine (Lys) are heavily involved in HA nucleation within extracellular matrix proteins such as collagen. Glu, Arg and Lys intake can also increase bone mineral density by stimulating growth hormone production. In vitro studies suggest that the role of AAs in controlling HA precipitation is affected by their mobility. While dissolved AAs are able to inhibit HA precipitation and growth by chelating Ca²⁺ and PO₄^3- ions or binding to nuclei of calcium phosphate and preventing their further growth, AAs bound to surfaces can promote HA precipitation by attracting Ca²⁺ and PO₄^3- ions and increasing the local supersaturation. Overall, the effect of AAs on HA precipitation is worth being investigated more, especially under conditions closer to the physiological ones, where the presence of other factors such as collagen, mineralization inhibitors, and cells heavily influences HA precipitation. A deeper understanding of the role of AAs in HA mineralization will increase our fundamental knowledge related to bone formation, and could lead to new therapies to improve bone regeneration in damaged tissues or cure pathological diseases caused by excessive mineralization in tissues such as cartilage, blood vessels and cardiac valves.

Keywords: amino acids; biomineralization; hydroxyapatite.

Figure 1.

Different pathways for HA precipitation in a bricks (HA) and mortar (ACP) configuration in presence of Glu and Gly. Reproduced from [40] with permission from the Royal Society of Chemistry.

Figure 2.

Scanning electron microscopy images of the HA crystals synthesized without any AAs (a) or in the presence of Gly (b), Ser (c), Asp (d) and Glu (d). Scale bar, 300 nm. Reproduced from [24] with permission from Elsevier.

Figure 3.

Schematic shows the reduced interfacial energy barrier between brushite (DCPD) and HA in the presence of acidic AAs. Reproduced from [32] with permission from the American Chemical Society. (Online version in colour.)

Figure 4.

Schematic shows the steps involved in the precipitation of HA in the presence of Asp-capped gold nanoparticles. Reproduced from [8] with permission from the American Chemical Society. (Online version in colour.)