title: Energetic basis for the molecular-scale organization of bone.
abstract: The remarkable properties of bone derive from a highly organized arrangement of coaligned nanometer-scale apatite platelets within a fibrillar collagen matrix. The origin of this arrangement is poorly understood and the crystal structures of hydroxyapatite (HAP) and the nonmineralized collagen fibrils alone do not provide an explanation. Moreover, little is known about collagen-apatite interaction energies, which should strongly influence both the molecular-scale organization and the resulting mechanical properties of the composite. We investigated collagen-mineral interactions by combining dynamic force spectroscopy (DFS) measurements of binding energies with molecular dynamics (MD) simulations of binding and atomic force microscopy (AFM) observations of collagen adsorption on single crystals of calcium phosphate for four mineral phases of potential importance in bone formation. In all cases, we observe a strong preferential orientation of collagen binding, but comparison between the observed orientations and transmission electron microscopy (TEM) analyses of native tissues shows that only calcium-deficient apatite (CDAP) provides an interface with collagen that is consistent with both. MD simulations predict preferred collagen orientations that agree with observations, and results from both MD and DFS reveal large values for the binding energy due to multiple binding sites. These findings reconcile apparent contradictions inherent in a hydroxyapatite or carbonated apatite (CAP) model of bone mineral and provide an energetic rationale for the molecular-scale organization of bone.
authors.affiliation: Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, CA 94720; Physical Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352;
authors.forename: Jinhui
authors.initials: J
authors.lastname: Tao
authors.affiliation: Department of Chemistry, University of South Alabama, Mobile, AL 36688;
authors.forename: Keith C
authors.initials: KC
authors.lastname: Battle
authors.affiliation: Qiushi Academy for Advanced Studies, Zhejiang University, Hangzhou, 310027 China; and.
authors.forename: Haihua
authors.initials: H
authors.lastname: Pan
authors.affiliation: Department of Chemistry, University of South Alabama, Mobile, AL 36688;
authors.forename: E Alan
authors.initials: EA
authors.lastname: Salter
authors.affiliation: Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, CA 94720; Department of Preventive and Restorative Dental Sciences, University of California, San Francisco, CA 94143.
authors.forename: Yung-Ching
authors.initials: YC
authors.lastname: Chien
authors.affiliation: Department of Chemistry, University of South Alabama, Mobile, AL 36688; awierzbicki@southalabama.edu james.deyoreo@pnnl.gov.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Wierzbicki
authors.affiliation: Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, CA 94720; Physical Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352; awierzbicki@southalabama.edu james.deyoreo@pnnl.gov.
authors.forename: James J
authors.initials: JJ
authors.lastname: De Yoreo
mesh_terms: D000818:Animals; D001665:Binding Sites; D001842:Bone and Bones / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D002417:Cattle; D003804:Dentin / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D017886:Durapatite / Q000737:chemistry / Q000378:metabolism; D004734:Energy Metabolism; D024022:Fibrillar Collagens / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D018625:Microscopy, Atomic Force; D046529:Microscopy, Electron, Transmission; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D049329:Nanostructures / Q000737:chemistry / Q000648:ultrastructure; D051381:Rats
chemical_list: D024022:Fibrillar Collagens; D017886:Durapatite
keywords: biomineralization; bone; dynamic force spectroscopy; protein–mineral interface