title: 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.
authors.affiliation: Department of Polymer Science, University of Akron, 170 University Ave, Akron, OH 44325, USA. Electronic address: zxu@uakron.edu.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Chemistry and Biochemistry, Rowan University, 201 Mullica Hill Rd, Glassboro, NJ 08028, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Polymer Science, University of Akron, 170 University Ave, Akron, OH 44325, USA.
authors.forename: Weilong
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Department of Polymer Science, University of Akron, 170 University Ave, Akron, OH 44325, USA.
authors.forename: Ziqiu
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Polymer Science, University of Akron, 170 University Ave, Akron, OH 44325, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Landis
authors.affiliation: Department of Chemistry and Theoretical Chemistry Institute, University of Wisconsin-Madison, 1101 University Ave, Madison, WI 53706, USA.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Cui
authors.affiliation: Department of Polymer Science, University of Akron, 170 University Ave, Akron, OH 44325, USA; Integrated Bioscience Program, University of Akron, 170 University Ave, Akron, OH 44325, USA. Electronic address: sahai@uakron.edu.
authors.forename: Nita
authors.initials: N
authors.lastname: Sahai
mesh_terms: D001842:Bone and Bones / Q000378:metabolism; D002130:Calcium Phosphates / Q000737:chemistry*; D003094:Collagen / Q000378:metabolism*; D017886:Durapatite / Q000737:chemistry*; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D017433:Protein Structure, Secondary
chemical_list: D002130:Calcium Phosphates; D003094:Collagen; D017886:Durapatite; C020243:calcium phosphate
keywords: Biomineralization; Bone; Collagen fibril; Hydroxyapatite; Simulation