title: Hierarchical self-assembly of amelogenin and the regulation of biomineralization at the nanoscale.
abstract: Enamel is a highly organized hierarchical nanocomposite, which consists of parallel arrays of elongated apatitic crystallites forming an intricate three-dimensional microstructure. Amelogenin, the major extracellular matrix protein of dental enamel, regulates the formation of these crystalline arrays via cooperative interactions with forming mineral phase. Using cryoelectron microscopy, we demonstrate that amelogenin undergoes stepwise hierarchical self-assembly. Furthermore, our results indicate that interactions between amelogenin hydrophilic C-terminal telopeptides are essential for oligomer formation and for subsequent steps of hierarchical self-assembly. We further show that amelogenin assemblies stabilize mineral prenucleation clusters and guide their arrangement into linear chains that organize as parallel arrays. The prenucleation clusters subsequently fuse together to form needle-shaped mineral particles, leading to the formation of bundles of crystallites, the hallmark structural organization of the forming enamel at the nanoscale. These findings provide unique insight into the regulation of biological mineralization by specialized macromolecules and an inspiration for bottom-up strategies for the materials design.
authors.affiliation: Department of Oral Biology, Center for Craniofacial Regeneration, McGowan Institute for Regenerative Medicine, University of Pittsburgh, 3501 Terrace Street, PA 15261, USA.
authors.forename: Ping-An
authors.initials: PA
authors.lastname: Fang
authors.forename: James F
authors.initials: JF
authors.lastname: Conway
authors.forename: Henry C
authors.initials: HC
authors.lastname: Margolis
authors.forename: James P
authors.initials: JP
authors.lastname: Simmer
authors.forename: Elia
authors.initials: E
authors.lastname: Beniash
mesh_terms: D053523:Amelogenin / Q000378:metabolism* / Q000648:ultrastructure; D000818:Animals; D002113:Calcification, Physiologic / Q000502:physiology*; D002130:Calcium Phosphates / Q000378:metabolism; D020285:Cryoelectron Microscopy; D007091:Image Processing, Computer-Assisted; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*
chemical_list: D053523:Amelogenin; D002130:Calcium Phosphates; C020243:calcium phosphate