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

Abstract

Unravelling the processes of calcium phosphate formation is important in our understanding of both bone and tooth formation, and also of pathological mineralization, for example in cardiovascular disease. Serum is a metastable solution from which calcium phosphate precipitates in the presence of calcifiable templates such as collagen, elastin and cell debris. 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 phase. ACP formation is thought to proceed through prenucleation clusters--stable clusters that are present in solution already before nucleation--as was recently demonstrated for CaCO(3) (refs 15,16). However, the role of such nanometre-sized clusters as building blocks for ACP has been debated for many years. Here we demonstrate that the surface-induced formation of apatite from simulated body fluid starts with the aggregation of prenucleation clusters leading to the nucleation of ACP before the development of oriented apatite crystals.

Mineralization and non-ideality: on nature’s foundry

“…According to the conventional theory, nucleation in a homogenous supersaturated solution occurs via stochastic microscopic density fluctuations and a balance between the bulk and surface energy of an emerging phase (Frenkel 1939). However, recent studies indicate that ion-associates such as pre-nucleation clusters and liquid-like phases play vital roles in determining nucleation phenomena associated with several minerals (Bewernitz et al 2012;De Yoreo et al 2015;Dey et al 2010;Gebauer and Cölfen 2011;Gebauer et al 2008Gebauer et al , 2014Jolivet et al 2006;Wallace et al 2013). Potentiometric titration-based studies on CaCO 3 nucleation have identified distinct crowding niches leading to either enhanced or suppressed ion-association .…”

“…Mineralization performed in proximity of monolayers composed of amphiphilic molecules provide similar indications. The growth of mineral particles in simulated body fluid under a Langmuir monolayer of arachidic acid reveals distinct stages of mineral growth involving pre-nucleation clusters and amorphous particles (Cölfen 2010;Dey et al 2010). Since the mineral precursors associate with the monolayer surface, the interfacial distribution of monolayer constituents possibly influences nucleation and crystallization behavior.…”

Two‐Dimensional Hybrid Materials: Transferring Technology from Biology to Society

“…[22] With inspiration from biomineralization, organic-inorganic interactions at interfaces have been explored for the formation of 2D hybrids based on other biominerals such as calcium phosphate [23] or magnetite, [24] but also many studies have extended this approach to controlling the formation of typical engineering materials such as CdS, ZnS, PbS, CdSe, TiO 2 , as well as Au, Ag, and Pt nanoparticles. [25] In particular, from an application point of view it is interesting to point out that the formation of ordered assemblies of crystals with near-uniform sizes, shapes, and orientation as observed in the prismatic layer of the mollusk shell does not require a very precise templating structure.…”

Effect of fetal bovine serum on mineralization in silk fibroin scaffolds

“…Biominerals are hybrid structures composed of both minerals and organic components [4]. Mineral deposition starts by the formation of prenucleation clusters at a templating surface initiated by local supersaturation of ions [5,6]. The formation of these ion clusters is highly dependent on the fluid surrounding the underlying structure of the inorganic matrix [4,6].…”

“…Mineral deposition starts by the formation of prenucleation clusters at a templating surface initiated by local supersaturation of ions [5,6]. The formation of these ion clusters is highly dependent on the fluid surrounding the underlying structure of the inorganic matrix [4,6]. The proteins of the inorganic matrix interact with ions of the surrounding fluid and facilitate the formation of mineralized macromolecules [5].…”