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The predominant role of collagen in the nucleation, growth, structure and orientation of bone apatite

Nature Materials volume 11, pages 724–733 (2012)Cite this article

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Abstract

The involvement of collagen in bone biomineralization is commonly admitted, yet its role remains unclear. Here we show that type I collagen in vitro can initiate and orientate the growth of carbonated apatite mineral in the absence of any other vertebrate extracellular matrix molecules of calcifying tissues. We also show that the collagen matrix influences the structural characteristics on the atomic scale, and controls the size and the three-dimensional distribution of apatite at larger length scales. These results call into question recent consensus in the literature on the need for Ca-rich non-collagenous proteins for collagen mineralization to occur in vivo. Our model is based on a collagen/apatite self-assembly process that combines the ability to mimic the in vivo extracellular fluid with three major features inherent to living bone tissue, that is, high fibrillar density, monodispersed fibrils and long-range hierarchical organization.

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Figure 1: Comparison of collagen density and organization between in vitro models and bone.
Figure 2: Investigation of apatite formation and distribution in highly concentrated collagen matrices.
Figure 3: Investigation of the collagen/apatite structural relationship at the fibrillar level.
Figure 4: Structural investigation of CHA by solid-state NMR.
Figure 5: Characterization of the Coll(SBF) matrix.
Figure 6: Characterization of a Coll/CHA matrix with a gradient in collagen concentration, and the corresponding schematic representation of the apatite crystal/collagen fibril relationship in a 3D perspective.

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Acknowledgements

We dedicate this work to the memory of Y. Bouligand (1935–2011). This work was supported by the Agence Nationale de la Recherche (ANR) through the ANR-09-BLAN-0120-01 ‘NanoShap’ program and the DRITT-SAIC (UPMC). We thank G. Laurent and M. Selmane for technical assistance with the NMR spectrometer and WAXD experiments respectively; A. Anglo, C. Illoul and E. Jallot for preparation of TEM samples; S. Mann, J. Peron, F. Michaux and Ö. Sel for insightful discussions and critical suggestions; A. Galtayries for X-ray photoelectron spectroscopy experiments and IMM Recherche, especially L. Behr, for providing the fresh bone samples.

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Authors and Affiliations

  1. Laboratoire Chimie de la Matière Condensée de Paris, UMR 7574 CNRS, Université Pierre et Marie Curie, Collège de France, 11 place Marcelin Berthelot, 75231 Paris Cedex 05, France

    Yan Wang, Thierry Azaïs, Marc Robin, Anne Vallée, Chelsea Catania, Patrick Legriel, Florence Babonneau, Marie-Madeleine Giraud-Guille & Nadine Nassif

  2. URA 2185, Institut Pasteur, 28 rue du Docteur Roux, 75015 Paris, France

    Gérard Pehau-Arnaudet

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  1. Yan Wang
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Contributions

Y.W., T.A., M.R., C.C., P.L., G.P-A. and N.N. performed the research; F.B. looked for financial support for the project; Y.W., T.A., A.V., G.P-A., F.B., M-M.G-G. and N.N. analysed data; Y.W., T.A., C.C., A.V., M-M.G-G. and N.N. wrote the paper; N.N. designed the research.

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Correspondence to Marie-Madeleine Giraud-Guille or Nadine Nassif.

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Wang, Y., Azaïs, T., Robin, M. et al. The predominant role of collagen in the nucleation, growth, structure and orientation of bone apatite. Nature Mater 11, 724–733 (2012). https://doi.org/10.1038/nmat3362

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