The role of prenucleation clusters in surface-induced calcium phosphate crystallization


Unravelling the processes of calcium phosphate formation1,2,3,4 is important in our understanding of both bone and tooth formation5,6,7, and also of pathological mineralization, for example in cardiovascular disease8,9,10. Serum is a metastable solution from which calcium phosphate precipitates in the presence of calcifiable templates such as collagen, elastin and cell debris11,12. A pathological deficiency of inhibitors leads to the uncontrolled deposition of calcium phosphate. In bone and teeth the formation of apatite crystals is preceded by an amorphous calcium phosphate (ACP) precursor phase13,14. ACP formation is thought to proceed through prenucleation clusters—stable clusters that are present in solution already before nucleation—as was recently demonstrated for CaCO3 (refs 1516). However, the role of such nanometre-sized clusters as building blocks2 for ACP has been debated for many years. Here we demonstrate that the surface-induced formation of apatite from simulated body fluid17,18 starts with the aggregation of prenucleation clusters leading to the nucleation of ACP before the development of oriented apatite crystals.

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Figure 1: Stable prenuclation clusters in SBF.
Figure 2: CryoTEM imaging of different stages of the mineralization process.
Figure 3: Schematic representation of the different stages of surface-directed mineralization of calcium phosphate from SBF at 37 °C.


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Supported by the European Community (project code NMP4-CT-2006-033277) and the Netherlands Organization for Scientific Research (NWO). We are grateful to F. Nudelman for discussions and experimental assistance. We thank E. M. Pouget for her help in experimental design, F. L. Boogaard and J. J. van Roosmalen for their contribution to the three-dimensional reconstructions of the tomograms, M.M.R.M. Hendrix for his help with X-ray diffraction and P. T. K. Chin for providing the CdSe nanorods.

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A.D. carried out all experiments and cowrote the manuscript. P.H.H.B. and P.M.F. provided support with the cryoTEM. F.A.M. and J.W. provided SBF. G.W. and N.A.J.M.S. supervised the project and N.A.J.M.S. cowrote the manuscript. All authors discussed the results and revised the manuscript.

Corresponding author

Correspondence to Nico A. J. M. Sommerdijk.

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The authors declare no competing financial interests.

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Dey, A., Bomans, P., Müller, F. et al. The role of prenucleation clusters in surface-induced calcium phosphate crystallization. Nature Mater 9, 1010–1014 (2010).

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