Molecular mechanisms for intrafibrillar collagen mineralization in skeletal tissues. (January 2015) - Xu, Zhijun
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.