Energetic basis for the molecular-scale organization of bone

• Published in: Proceedings of the National Academy of Sciences - PNAS 2015-01, Vol.112 (2), p.326-331
• Main Authors: Tao, Jinhui, Battle, Keith C., Pan, Haihua, Salter, E. Alan, Chien, Yung-Ching, Wierzbicki, Andrzej, De Yoreo, James J.
• Format: Article
• Language: English
• Subjects: Animals; Binding Sites; biomineralization; Blood platelets; bone; Bone and Bones - chemistry; Bone and Bones - metabolism; Bone and Bones - ultrastructure; Cattle; Collagen; Crystal structure; Dentin - chemistry; Dentin - metabolism; Dentin - ultrastructure; Durapatite - chemistry; Durapatite - metabolism; dynamic force spectroscopy; Energy Metabolism; Fibrillar Collagens - chemistry; Fibrillar Collagens - metabolism; Fibrillar Collagens - ultrastructure; Humans; INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; Microscopy, Atomic Force; Microscopy, Electron, Transmission; Models, Molecular; Molecular Dynamics Simulation; Nanostructures - chemistry; Nanostructures - ultrastructure; Physical Sciences; protein-miuneral interface; Rats; Simulation; Single crystals; Transmission electron microscopy
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1404481112

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. Significance The remarkable mechanical properties of bone are determined by the organization and strength of binding at the mineral–collagen interface. Although the process through which collagen becomes mineralized has been extensively studied, little is known about the mechanisms or energetics that underlie the organization of this mineral–matrix composite. Combining molecular-scale imaging and analyses of collagen adsorption on four bone-related calcium phosphate phases, single-molecule force measurements and molecular simulations of collagen binding to hydroxyapatite, and electron microscopy analyses of bone and dentine, we determine the magnitude and chemistry of collagen–hydroxyapatite binding and show that calcium-deficient apatite is the only phase consistent with observed structural relationships.