Nano-Imaging Reveals Links to Regulation of Bone Mineralization

A team of bioengineers applied a hi-tech nano-imagining technique to determine the mechanisms involved in the initialization and regulation of the process of bone mineralization.

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.


To develop a better understanding of the mechanisms underlying bone mineralization, investigators at Washington University (St. Louis, Mo, USA) turned to the Advanced Photon Source at the Argonne National Laboratory (Lemont, IL, USA). They used this tool to apply the technique of in situ small-angle X-ray (SAXS) scattering in order to study calcium phosphate nucleation in the collagen gap (a space about two nanometers high by 40 nanometers wide).

They investigators described in the March 6, 2018, online edition of the journal Nature Communications the results they had obtained using in situ X-ray scattering observations and classical nucleation theory. They reported obtaining nucleation energy barriers to intra- and extrafibrillar mineralization (IM and EM). Polyaspartic acid, an extrafibrillar nucleation inhibitor, increased interfacial energies between nuclei and mineralization fluids. In contrast, the confined gap spaces inside collagen fibrils lowered the energy barrier by reducing the reactive surface area of nuclei, decreasing the surface energy penalty. The confined gap geometry, therefore, guided the two-dimensional morphology and structure of bioapatite and changed the nucleation pathway by reducing the total energy barrier.

“When we understand how new bone forms, we can modulate where it should form,” said senior author Dr. Young-Shin Jun, professor of energy and environmental and chemical engineering at Washington University. “Previously, we thought that collagen fibrils could serve as passive templates, however, this study confirmed that collagen fibrils play an active role in biomineralization by controlling nucleation pathways and energy barriers. If we can tweak the chemistry and send signals to form bone minerals faster or stronger, that would be helpful to the medical field.”

“Confined space is a somewhat exotic space that we have not explored much, and we are always thinking about new material formation without any limitation of space,” said Dr. Jun. “However, there are so many confined spaces, such as pores in geomedia in subsurface environments or in water filtration membranes, where calcium carbonate or calcium sulfate form as scale. This paper is a snapshot of one health aspect, but the new knowledge can be applied broadly to energy systems and water systems.”

Related Links:
Washington University
Argonne National Laboratory