The role of confined collagen geometry in decreasing nucleation energy barriers to intrafibrillar mineralization

Doyoon Kim,Young-Shin Jun,Stavros Thomopoulos,Byeongdu Lee

doi:10.1038/s41467-018-03041-1

Abstract

Mineralization of collagen is critical for the mechanical functions of bones and teeth. Calcium phosphate nucleation in collagenous structures follows distinctly different patterns in highly confined gap regions (nanoscale confinement) than in less confined extrafibrillar spaces (microscale confinement). Although the mechanism(s) driving these differences are still largely unknown, differences in the free energy for nucleation may explain these two mineralization behaviors. Here, we report on experimentally obtained nucleation energy barriers to intra- and extrafibrillar mineralization, using in situ X-ray scattering observations and classical nucleation theory. Polyaspartic acid, an extrafibrillar nucleation inhibitor, increases interfacial energies between nuclei and mineralization fluids. In contrast, the confined gap spaces inside collagen fibrils lower the energy barrier by reducing the reactive surface area of nuclei, decreasing the surface energy penalty. The confined gap geometry, therefore, guides the two-dimensional morphology and structure of bioapatite and changes the nucleation pathway by reducing the total energy barrier.

Highlights

Mineralization of collagen is critical for the mechanical functions of bones and teeth
Nudelman et al showed that a specific band position in the gap region of collagen with a net positive charge can attract net negatively charged amorphous calcium phosphate (ACP) nuclei in the presence of polyaspartic acid, which is a well-known substitute for noncollagenous proteins (NCPs) in biomimetic experiments[20]
A heterogeneous nucleation model in classical nucleation theory (CNT) has been adopted to explain how the interfacial energy and nucleation barrier decrease in the presence of collagen, by assuming the collagen is a flat substrate for hemispherical particle formation[25,35,36,37]

Summary

Introduction

Mineralization of collagen is critical for the mechanical functions of bones and teeth. Recent studies have investigated nucleation in confined nanoscale pore spaces[1,5,6], where the physicochemical properties, such as the melting point or crystal polymorphism[6], of the minerals formed in the pores are clearly distinct from their bulk phase counterparts. These findings provide a better understanding of biominerals. Nudelman et al showed that a specific band position in the gap region of collagen with a net positive charge can attract net negatively charged amorphous calcium phosphate (ACP) nuclei in the presence of polyaspartic acid (pAsp), which is a well-known substitute for NCPs in biomimetic experiments[20]. The formation of prenucleation clusters, a Extrafibrillar mineralization (unconfined nucleation) b

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Results

Conclusion