Liquid-Liquid Phase Separation in Nucleation Process of Biomineralization

Abstract

Biomineralization is a typical interdisciplinary subject attracting biologists, chemists, and geologists to figure out its potential mechanism. A mounting number of studies have revealed that the classical nucleation theory is not suitable for all nucleation process of biominerals, and phase-separated structures such as polymer-induced liquid precursors (PILPs) play essential roles in the non-classical nucleation processes. These structures are able to play diverse roles biologically or pathologically, and could also give inspiring clues to bionic applications. However, a lot of confusion and dispute occurred due to the intricacy and interdisciplinary nature of liquid precursors. Researchers in different fields may have different opinions because the terminology and current state of understanding is not common knowledge. As a result, our team reviewed the most recent articles focusing on the nucleation processes of various biominerals to clarify the state-of-the-art understanding of some essential concepts and guide the newcomers to enter this intricate but charming field.

The Role of Intrinsically Disordered Proteins in Liquid–Liquid Phase Separation during Calcium Carbonate Biomineralization

“…These factors include surface wettability or inhomogeneity, which affect the nucleation barrier and the nucleation rate. Another difficulty stems from the interdisciplinary nature of this phenomenon, which has caused diversity in the terminology used by researchers from different fields [ 20 , 96 , 97 ].…”

“…Interestingly, recent studies increasingly use LLPS to explain the behaviour of calcium carbonate-containing solutions in the context of the mineralization mechanism [ 20 ]. Due to problems in determining the thermodynamics of the transient clusters that form during the nucleation process, molecular dynamics simulations were used to investigate the initial stability of the clusters with respect to the composition of the solution and formation pathway.…”

“…( A ) Schematic presentation of events occurring during the formation of crystals from the bulk liquid to crystalline pathways according to classical theory (blue) and multistep pathways (red). ( B ) Comparison of free energy along the pathway of crystal nucleation following the classical nucleation mechanism (blue) and multistep pathways (red) [ 20 , 108 ].…”

“…Moreover, further experimental results concerning calcium carbonate mineralization presented prenucleation clusters as a key precursor phase in mineral formation [ 19 ]. Currently, a concept that involves the formation of dense liquid precursors of amorphous calcium carbonate (ACC) via LLPS has become a popular topic of investigation [ 20 , 21 ].…”

In Vitro Biodegradation of a-C:H:SiOx Films on Ti-6Al-4V Alloy

“…The ion precipitation from solutions onto hard surfaces and the formation of grains of sodium chloride are multifactorial mechanisms, which are still hypothetic [51]. Based on the results, it can be concluded that:…”