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Collagen intrafibrillar mineralization as a result of the balance between osmotic equilibrium and electroneutrality

Nature Materials volume 16, pages 370–378 (2017)Cite this article

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Abstract

Mineralization of fibrillar collagen with biomimetic process-directing agents has enabled scientists to gain insight into the potential mechanisms involved in intrafibrillar mineralization. Here, by using polycation- and polyanion-directed intrafibrillar mineralization, we challenge the popular paradigm that electrostatic attraction is solely responsible for polyelectrolyte-directed intrafibrillar mineralization. As there is no difference when a polycationic or a polyanionic electrolyte is used to direct collagen mineralization, we argue that additional types of long-range non-electrostatic interaction are responsible for intrafibrillar mineralization. Molecular dynamics simulations of collagen structures in the presence of extrafibrillar polyelectrolytes show that the outward movement of ions and intrafibrillar water through the collagen surface occurs irrespective of the charges of polyelectrolytes, resulting in the experimentally verifiable contraction of the collagen structures. The need to balance electroneutrality and osmotic equilibrium simultaneously to establish Gibbs–Donnan equilibrium in a polyelectrolyte-directed mineralization system establishes a new model for collagen intrafibrillar mineralization that supplements existing collagen mineralization mechanisms.

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Figure 1: Cryogenic TEM images and cryo-electron tomography of collagen fibrils mineralized by PAH-ACP.
Figure 2: Conventional TEM of mineralization of reconstituted collagen fibrils by PAH-ACP (single-layer collagen mineralization model).
Figure 3: Cationic collagen model of PAH-ACP intrafibrillar mineralization.
Figure 4: The effects of inclusion of a short-chain polyamine (spermine) on collagen mineralization with PAH-ACP.
Figure 5: Molecular dynamics simulations.
Figure 6: Molecular dynamics simulations of the movement of ions, water molecules and mineralization precursors that are simplified as Ca ions across the contracted collagen structures in the presence of polyanionic and polycationic electrolytes, following the introduction of Ca ions into the system.

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Acknowledgements

This work was supported by grant 2015AA020942 from the National High Technology Research and Development Program of China, grant R01 DE015306-06 from NIDCR, grants 81400555, 81130078, 81671012 and 81530050 from NSFC, program IRT13051 from Changjiang Scholars and Innovative Research Team in University and Young Elite Scientist Sponsorship Program by CAST. We thank L. B. Gower (University of Florida, Florida, USA) for discussion of some of the results.

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Author notes

  1. Li-na Niu and Sang Eun Jee: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Prosthodontics, State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Oral Diseases, School of Stomatology, The Fourth Military Medical University, Xi’an 710032, China

    Li-na Niu, Kai Jiao & Ji-hua Chen

  2. School of Materials Science and Engineering, Georgia Institute of Technology, Atlanta, Georgia 30332, USA

    Sang Eun Jee & Seung Soon Jang

  3. Department of Biological Structure, University of Washington, Seattle, Washington 98195, USA

    Lige Tonggu, Mo Li & Liguo Wang

  4. Frontier Institute of Science and Technology, State Key Laboratory for Mechanical Behavior of Materials, Xi’an Jiaotong University, Xi’an 710054, China

    Yao-dong Yang & Ji-hong Bian

  5. Department of Biomedical and Neuromotor Sciences, DIBINEM, University of Bologna, 40125 Bologna, Italy

    Lorenzo Breschi

  6. The Dental College of Georgia, Augusta University, Augusta, Georgia 30912, USA

    David H. Pashley & Franklin R. Tay

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  1. Li-na Niu
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Contributions

L.-n.N. and K.J. performed the mineralization experiments and analytical part of the study and wrote the manuscript. S.E.J. and S.S.J. contributed to the molecular dynamic simulation. L.T., M.L. and L.W. performed cryo-TEM examination. J.-h.B. and Y.-d.Y. contributed to the atomic force microscopy. J.-h.C., L.B. and D.H.P. provided advice on the experimental design and edited the manuscript. F.R.T. performed ultramicrotomy, TEM examination, supervised the project and wrote the manuscript. All authors discussed the results and revised the manuscript.

Corresponding authors

Correspondence to Seung Soon Jang, Ji-hua Chen or Franklin R. Tay.

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Niu, Ln., Jee, S., Jiao, K. et al. Collagen intrafibrillar mineralization as a result of the balance between osmotic equilibrium and electroneutrality. Nature Mater 16, 370–378 (2017). https://doi.org/10.1038/nmat4789

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