This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Bone is an excellent structural material due to its high strength, stiffness, and fracture toughness and low weight. These superior properties are due in part to the hierarchical structure of bone ranging from atomic to macroscopic levels. In this proposed research we model bone from atomic level to nanoscale. Bone will be represented as a composite consisting of collagen, hydroxyapatite crystals, water, and non-collagenous proteins. The analysis will be done using atomic level simulations involving molecular dynamics and computational micromechanics-based models using a finite element method. MD simulations will be performed using the NAMD package with CHARMM force field. VMD software will also be used to visualize all molecular interactions. The system will be first equilibrated in the Isothermal and isobaric ensemble (NPT). The simulations will be done in different steps as follows 1. Modeling the collagen molecule which is a triple helix molecule with non-helical ends that are N- or C-telopeptides. 2. Adding water molecules to get the solvated collagen. 3. Pulling the solvated tropocollagen molecule to obtain its force-extension curves and assess the strength and the stiffness of the molecule. 4. Adding cross-linking between two or more collagen molecules at different locations. 5. Adding non-collagenous proteins. There are a variety of non-collagenous proteins in bone such as osteocalcin, osteopontin, proteoglycan, and others. Here, we intend to model only one or two of these proteins. 6. Adding hydroxyapatite mineral crystals. When subjected to load, the interactions at the interface between HAP and collagen may significantly affect the overall mechanics of the collagen molecule and this phenomenon is not well understood yet. Performing MD simulations, we will obtain the information about the interaction between different components of bone and we will be able to answer some of the open issues about the geometry, structure, and properties of bone at the nanostructural level. The micromechanics-based analytical and finite element models, which are the continuum-based mechanics tools, will be used to calculate the local fields and mechanical properties of bone including ultimate strength and strain, effective elastic modulus, nonlinear stress-strain curve, fracture toughness, fracture mechanisms, and other parameters. The atomic-based molecular dynamics approach will be applied to understand the interaction between molecules with different chemical composition. The results from atomic simulations will be used as inputs in finite element models. Thus, in this project we will combine the continuum and atomic approaches to gain a better understanding of the physical, structural, and mechanical properties of bone.

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
Biotechnology Resource Grants (P41)
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Special Emphasis Panel (ZRG1-BCMB-Q (40))
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Carnegie-Mellon University
Biostatistics & Other Math Sci
Schools of Arts and Sciences
United States
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