Matrix macromolecules in hard tissues control the nucleation and hierarchical assembly of hydroxyapatite.
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.
Gajjeraman
Sivakumar
S
Department of Oral Biology, University of Illinois, Chicago, Illinois 60612, USA.
Narayanan
Karthikeyan
K
Hao
Jianjun
J
Qin
Chunlin
C
George
Anne
A
D000818:Animals; D001696:Biomechanical Phenomena; D002113:Calcification, Physiologic / Q000502:physiology*; D002130:Calcium Phosphates / Q000737:chemistry / Q000378:metabolism; D024042:Collagen Type I / Q000737:chemistry / Q000378:metabolism; D003460:Crystallization; D017886:Durapatite / Q000737:chemistry* / Q000378:metabolism*; D004548:Elasticity; D005109:Extracellular Matrix / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D016326:Extracellular Matrix Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006244:Hardness; D008855:Microscopy, Electron, Scanning; D010750:Phosphoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013059:Spectrum Analysis, Raman; D014961:X-Ray Diffraction
D002130:Calcium Phosphates; D024042:Collagen Type I; C081635:Dmp1 protein, rat; D016326:Extracellular Matrix Proteins; D010750:Phosphoproteins; D011994:Recombinant Proteins; C519480:amorphous calcium phosphate; D017886:Durapatite