Branched Polymeric Prenucleation Assemblies Initiate Calcium Phosphate Precipitation

Author(s)

Ertan Turhan, Ieva Goldberga, Christopher Pötzl, Waldemar Keil, Jean Michel Guigner, Martin F.T. Haßler, Herwig Peterlik, Thierry Azaïs, Dennis Kurzbach

Abstract

The formation of crystalline calcium phosphate (CaP) has recently gained ample attention as it does not follow the classic nucleation-and-growth mechanism of solid formation. Instead, the precipitation mechanisms can involve numerous intermediates, including soluble prenucleation species. However, structural features, stability, and transformation of such solution-state precursors remain largely undisclosed. Herein, we report a detailed and comprehensive characterization of the sequential events involved in calcium phosphate crystallization starting from the very early prenucleation stage. We integrated an extensive set of time-resolved methods, including NMR, turbidimetry, SAXS, cryo-TEM, and calcium-potentiometry to show that CaP nucleation is initiated by the transformation of “branched” polymeric prenucleation assemblies into amorphous calcium phosphate spheres. Such a mineralization process starts with the spontaneous formation of so-called nanometric prenucleation clusters (PNCs) that later assemble into those branched polymeric assemblies without calcium ion uptake from the solution. Importantly, the branched macromolecular species are invisible to many techniques (NMR, turbidity, calcium-potentiometry) but can readily be evidenced by time-resolved SAXS. We find that these polymeric assemblies constitute the origin of amorphous calcium phosphate (ACP) precipitation through an unexpected process: spontaneous dissolution is followed by local densification of 100-200 nm wide domains leading to ACP spheres of similar size. Finally, we demonstrate that the timing of the successive events involved in the CaP mineralization pathway can be kinetically controlled by the Ca²⁺/P_i molar ratio, such that the lifetime of the soluble transient species can be increased up to hours when decreasing it.

Organisation(s)

Department of Biological Chemistry, Dynamics of Condensed Systems, Faculty Center for Nano Structure Research, NMR Centre

External organisation(s)

Université Paris VI - Pierre-et-Marie-Curie, Vienna Doctoral School in Chemistry (DoSChem)

Journal

Journal of the American Chemical Society

Volume

146

Pages

25614-25624

No. of pages

11

ISSN

0002-7863

DOI

https://doi.org/10.1021/jacs.4c07325

Publication date

2024

Peer reviewed

Yes

Austrian Fields of Science 2012

103006 Chemical physics, 104017 Physical chemistry, 105113 Crystallography

ASJC Scopus subject areas

Catalysis, General Chemistry, Biochemistry, Colloid and Surface Chemistry

Portal url

https://ucrisportal.univie.ac.at/en/publications/5b599974-8601-427b-9e61-7dcce365ab02