This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.We have created a series of finite element models, using Abaqus software on Datastar, of so-called secondary osteons, basic units of human skeleton which .measure up to 0.5 mm in length. The models include ellipsoids that simulate osteocyte lacunae. The number of the simulated lacunae ranges between 7 and 70. The positions of lacunae can be chosen by the operator or assigned to follow experimentally observed distributions in the osteon. The mechanical properties of the elements adjacent to the ellipsoids simulate the collagen-apatite orientation that we have observed in isolated lamellar specimens under confocal microscopy. We have completed the simulation of the experimental mechanical behavior of osteon specimens under tension and compression in relation to collagen-apatite orientation and presence of porosity during the elastic phase. The current models use 464,800 twenty-node elements. In the current models, the collagen-apatite orientation can be assigned to each element at the interface between lacuna and matrix. As the number of lacunae increases, both the Maple program that we use as precursor to Abaqus and the Abaqus job become increasingly time-consuming. For an osteon with 7 lacunae, Maple takes 30 min to generate the input files for the Abaqus job and the job on Datastar takes 5 days. We use also Abaqus cae for debugging and visualization of models. Our work is described in a paper that will be submitted soon to the Journal of Biomechanics. We see that the preferential orientation reduces the stress in comparison to homogeneous models. We infer that the preferential orientation optimizes the mechanical function of the tissue by delaying micro-crack formation. Now we propose the simulation of tension and compression loading beyond the elastic phase and of torsional loading around the osteon axis within the elastic phase, observed in the laboratory (Ascenzi et al., Journal of Biomechanics, 40, 2619, 2007). The body of geometrical and material information amassed in each model necessitates the supercomputer capability. The prediction of bone fractures in patients is a high priority goal for the National Institutes of Health and the American Society of Bone and Mineral Research. Because bone density alone does not allow assessment of bone quality and subsequent fracture prediction, microstructural parameters such as collagen-apatite orientation and porosity are investigated. The PI leads the worlds only laboratory which routinely accomplishes: (1) isolation, microscopy analysis and testing of single microstructures of controllable collagen-apatite orientation and porosity; and (2) modeling of microstructures for mechanical testing simulation. We intend to create a series of increasingly sophisticated models to better simulate and understand the behavior of microstructure. The PIs work is amassing a growing database of morphometry data from bone micro-structures obtained from donors of specific age, gender and pathologies that affect bone quality. We use Maple software to create the input files to be processed by Abaqus. Such programs reach into the database to create virtual microstructures that respect biological variation.

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
Biotechnology Resource Grants (P41)
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Carnegie-Mellon University
Biostatistics & Other Math Sci
Schools of Arts and Sciences
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Simakov, Nikolay A; Kurnikova, Maria G (2018) Membrane Position Dependency of the pKa and Conductivity of the Protein Ion Channel. J Membr Biol 251:393-404
Yonkunas, Michael; Buddhadev, Maiti; Flores Canales, Jose C et al. (2017) Configurational Preference of the Glutamate Receptor Ligand Binding Domain Dimers. Biophys J 112:2291-2300
Hwang, Wonmuk; Lang, Matthew J; Karplus, Martin (2017) Kinesin motility is driven by subdomain dynamics. Elife 6:
Earley, Lauriel F; Powers, John M; Adachi, Kei et al. (2017) Adeno-associated Virus (AAV) Assembly-Activating Protein Is Not an Essential Requirement for Capsid Assembly of AAV Serotypes 4, 5, and 11. J Virol 91:
Murty, Vishnu P; Calabro, Finnegan; Luna, Beatriz (2016) The role of experience in adolescent cognitive development: Integration of executive, memory, and mesolimbic systems. Neurosci Biobehav Rev 70:46-58
Subramanian, Sandeep; Chaparala, Srilakshmi; Avali, Viji et al. (2016) A pilot study on the prevalence of DNA palindromes in breast cancer genomes. BMC Med Genomics 9:73
Ramakrishnan, N; Tourdot, Richard W; Radhakrishnan, Ravi (2016) Thermodynamic free energy methods to investigate shape transitions in bilayer membranes. Int J Adv Eng Sci Appl Math 8:88-100
Zhang, Yimeng; Li, Xiong; Samonds, Jason M et al. (2016) Relating functional connectivity in V1 neural circuits and 3D natural scenes using Boltzmann machines. Vision Res 120:121-31
Lee, Wei-Chung Allen; Bonin, Vincent; Reed, Michael et al. (2016) Anatomy and function of an excitatory network in the visual cortex. Nature 532:370-4
Jurkowitz, Marianne S; Patel, Aalapi; Wu, Lai-Chu et al. (2015) The YhhN protein of Legionella pneumophila is a Lysoplasmalogenase. Biochim Biophys Acta 1848:742-51

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