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Nucleation of apatite crystals in vitro by self-assembled dentin matrix protein 1

Nature Materials volume 2, pages 552–558 (2003)Cite this article

Abstract

Bones and teeth are biocomposites that require controlled mineral deposition during their self-assembly to form tissues with unique mechanical properties. Acidic extracellular matrix proteins play a pivotal role during biomineral formation. However, the mechanisms of protein-mediated mineral initiation are far from understood. Here we report that dentin matrix protein 1 (DMP1), an acidic protein, can nucleate the formation of hydroxyapatite in vitro in a multistep process that begins by DMP1 binding calcium ions and initiating mineral deposition. The nucleated amorphous calcium phosphate precipitates ripen and nanocrystals form. Subsequently, these expand and coalesce into microscale crystals elongated in the c-axis direction. Characterization of the functional domains in DMP1 demonstrated that intermolecular assembly of acidic clusters into a β-sheet template was essential for the observed mineral nucleation. Protein-mediated initiation of nanocrystals, as discussed here, might provide a new methodology for constructing nanoscale composites by self-assembly of polypeptides with tailor-made peptide sequences.

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Figure 1: Mineral characterization.
Figure 2: Sequential appearance of deposited particles accompanying the hydroxyapatite nucleation and growth process.
Figure 3: Apatite crystallization process characterized by high-resolution TEM.
Figure 4: Calcium-induced self-assembly of peptides D1A and D1B and their function in mineral nucleation.
Figure 5: Characterization of peptides pA and pB.

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Acknowledgements

We thank our colleagues Naomi Eidelmann for providing the standard hydroxyapatite, Nigel Browning and Steve Weiner for their valuable comments and insights. This research was supported by National Institutes of Health grants DE 11657 & DE 13836.

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Authors and Affiliations

  1. Department of Oral Biology (M/C 690), University of Illinois at Chicago, Chicago, 60612, Illinois, USA

    Gen He & Anne George

  2. Department of Cell and Molecular Biology, Northwestern University, Chicago, 60611, Illinois, USA

    Tom Dahl & Arthur Veis

Authors
  1. Gen He
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  2. Tom Dahl
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  4. Anne George
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Correspondence to Anne George.

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Supplementary information

41563_2003_BFnmat945_MOESM1_ESM.pdf

Supplementary Information: Hypothetical model: A periodic surface with high calcium-binding capacity facilitate the assembly of Posner's cluster and hydroxyapatite nucleation. (PDF 372 kb)

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He, G., Dahl, T., Veis, A. et al. Nucleation of apatite crystals in vitro by self-assembled dentin matrix protein 1. Nature Mater 2, 552–558 (2003). https://doi.org/10.1038/nmat945

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