Molecular mechanisms for intrafibrillar collagen mineralization in skeletal tissues
Abstract
The critical role of the self-assembled structure of collagen in skeletal mineralization is long recognized, yet the angstrom to tens of nanometers length-scale nucleation mechanism of calcium phosphate mineral (Ca-Pi) remains unclear. Here, by constructing three-dimensional structure of collagen fibril, we report direct computational evidence of intrafibrillar Ca-Pi nucleation in the collagen matrix and illustrate the crucial role of charged amino acid sidechains of collagen molecules in nucleation. The all-atom Hamiltonian replica exchange molecular dynamics simulation shows that these charged sidechains are oriented toward the fibril "hole zones" and significantly template nucleation with amorphous Ca-Pi phase, ∼1.3-1.6 nm in size, thus explaining the empirical observations that Ca-Pi nucleates principally in these regions. We also show that the low water density of about 0.70 g cm(-3) in these zones may further benefit nucleation by lowering the enthalpic penalty for ion desolvation. This work provides insight, at the atomistic level, into the nucleation mechanism of bone crystals within a collagen matrix for understanding mineral deposition, interpreting mineralization experiments and guiding the design of new implantable materials.
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Evidence Hub reads this as a simulation / modelling, done in computer models (in silico), not in people. Its evidence level is 5 of 5 (Very low · case / narrative / animal / in vitro / in silico). Case reports, narrative reviews, and animal, cell or computer-model studies give the weakest evidence for human health.
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