Matrix Macromolecules in Hard Tissues Control the Nucleation and Hierarchical Assembly of Hydroxyapatite

Abstract

Biogenic minerals found in teeth and bones are synthesized by precise cell-mediated mechanisms. They have superior mechanical properties due to their complex architecture. Control over biomineral properties can be accomplished by regulation of particle size, shape, crystal orientation, and polymorphic structure. In many organisms, biogenic minerals are assembled using a transient amorphous mineral phase. Here we report that organic constituents of bones and teeth, namely type I collagen and dentin matrix protein 1 (DMP1), are effective crystal modulators. They control nucleation of calcium phosphate polymorphs and the assembly of hierarchically ordered crystalline composite material. Both full-length recombinant DMP1 and post-translationally modified native DMP1 were able to nucleate hydroxyapatite (HAP) in the presence of type I collagen. However, the N-terminal domain of DMP1 (amino acid residues 1-334) inhibited HAP formation and stabilized the amorphous phase that was formed. During the nucleation and growth process, the initially formed metastable amorphous calcium phosphate phase transformed into thermodynamically stable crystalline hydroxyapatite in a precisely controlled manner. The organic matrix-mediated controlled transformation of amorphous calcium phosphate into crystalline HAP was confirmed by x-ray diffraction, selected area electron diffraction pattern, Raman spectroscopy, and elemental analysis. The mechanical properties of the protein-mediated HAP crystals were also determined as they reflect the material structure. Such understanding of biomolecule controls on biomineralization promises new insights into the controlled synthesis of crystalline structures.

Amelogenesis Imperfecta and Other Biomineralization Defects in Fam20a and Fam20c Null Mice

“…matrix-specific precipitation of calcium phosphate on its own but relies on several different noncollagenous proteins that control nucleation and initial progression of mineralization. 31,32,45,107 In contrast, enamel mineralization takes place within a noncollagenous protein matrix that is secreted by ameloblasts of epithelial origin. This enamel matrix consists of specialized proteins that regulate the structural development and mineralization of enamel.…”

Identification of Full-Length Dentin Matrix Protein 1 in Dentin and Bone

“…Based on the obvious differences in their biochemical features, it is logical to hypothesize that these variants may have distinct functions and play different roles in biomineralization. In vitro mineralization studies have demonstrated that the COOH-terminal fragment promotes mineralization by acting as a nucleator for hydroxyapatite formation [14][15][16]. Information regarding the biological functions of the NH 2 -terminal fragment and DMP1-PG is lacking.…”

Hierarchically nanostructured hydroxyapatite: hydrothermal synthesis, morphology control, growth mechanism, and biological activity

“…Some successful methods including emulsion, 39,40 hydrothermal method, 41,42 solvothermal method, 43 sonochemical precipitation, 44 hard-template method, 45 sol-gel method, 46 biomimetic method, 47,48 and microwave irradiation 49 have been employed in the synthesis of HA. Gajjeraman et al 50 used organic constituents of bones and teeth to control the nucleation and assembly of hierarchical HA. Wang et al 51 reported the fabrication of HA nanorods by tuning the interfaces between surfactants and the central atoms of HA based on the liquid-solid-solution mechanism.…”