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Sci Adv ; 5(3): eaav9075, 2019 03.
Article in English | MEDLINE | ID: mdl-30989106

ABSTRACT

Contemporary models of intrafibrillar mineralization mechanisms are established using collagen fibrils as templates without considering the contribution from collagen-bound apatite nucleation inhibitors. However, collagen matrices destined for mineralization in vertebrates contain bound matrix proteins for intrafibrillar mineralization. Negatively charged, high-molecular weight polycarboxylic acid is cross-linked to reconstituted collagen to create a model for examining the contribution of collagen-ligand interaction to intrafibrillar mineralization. Cryogenic electron microscopy and molecular dynamics simulation show that, after cross-linking to collagen, the bound polyelectrolyte caches prenucleation cluster singlets into chain-like aggregates along the fibrillar surface to increase the pool of mineralization precursors available for intrafibrillar mineralization. Higher-quality mineralized scaffolds with better biomechanical properties are achieved compared with mineralization of unmodified scaffolds in polyelectrolyte-stabilized mineralization solution. Collagen-ligand interaction provides insights on the genesis of heterogeneously mineralized tissues and the potential causes of ectopic calcification in nonmineralized body tissues.


Subject(s)
Biomimetic Materials/metabolism , Calcification, Physiologic , Collagen/metabolism , Ligands , Biomimetics/methods , Extracellular Matrix/metabolism , Humans , Mesenchymal Stem Cells/metabolism , Microscopy, Electron/methods , Minerals/metabolism , Models, Molecular , Molecular Dynamics Simulation , Polyelectrolytes/metabolism , Tissue Scaffolds
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