Mechanisms of Load-Deformation Behavior of Molecular Collagen in Hydroxyapatite-Tropocollagen Molecular System: Steered Molecular Dynamics Study
Publication: Journal of Engineering Mechanics
Volume 135, Issue 5
Abstract
Bone is a widely studied structure due to its important function in the human body and also for its unique mechanical properties, which depend upon several factors, such as, its hierarchal structure, its constituents, degree of interactions between different constituents, etc. The major constituents of bone are collagen and hydroxyapatite (HAP). In this work, the load-carrying behavior of collagen is evaluated using steered molecular dynamics simulations. It is observed that the mineral HAP influences the load-deformation behavior of collagen. The collagen molecule (tropocollagen) requires more energy to deform when it is in close proximity of HAP. The reasons for a typical load-deformation behavior are also analyzed. It is observed that with stretching of the tropocollagen, first hydrogen bonds between the tropocollagen chains break, as a result of which more water molecules start interacting with chains. HAP significantly alters the interaction between tropocollagen and water. The load-carrying behavior of tropocollagen at different loading rates is also analyzed by pulling collagen at different velocities. These simulations give important information about the molecular mechanics of collagen and are also useful for the development of novel biomimetic artificial implant materials.
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Acknowledgments
This research is partially funded by a grant from the National Science Foundation (CAREER No. NSF0132768). The computational resources are provided by Teragrid and National Center of Superconducting applications (NCSA) at the University of Illinois at Urbana-Champaign (UIUC) MRAC (UNSPECIFIEDDMR No. 06005). Dr. Gregory H. Wettstein and Francis Larson of NDSU Center for High Performance Computing NDSU are acknowledged for hardware support. The first writer would like to acknowledge support from North Dakota EPSCoR for doctoral dissertation fellowship.
References
Beck, K., and Brodsky, B. (1998). “Supercoiled protein motifs: The collagen triple-helix and the a-helical coiled coil.” J. Struct. Biol., 122(1/2), 17–29.
Bertaut, F. (1958). “The electrostatic term of the surface energy.” Acad. Sci., Paris, C. R., 246(50), 3447–50.
Bhowmik, R., Katti, K. S., and Katti, D. R. (2007a). “Mechanics of molecular collagen is influenced by hydroxyapatite in natural bone.” J. Mater. Sci., 42(21), 8795–8803.
Bhowmik, R., Katti, K. S., and Katti, D. R. (2007b). “Molecular dynamics simulation of hydroxyapatite-polyacrylic acid interfaces.” Polymer, 48, (2), 664–674.
Bhowmik, R., Katti, K. S., Verma, D., and Katti, D. R. (2007c). “Probing molecular interactions in bone biomaterials: Through molecular dynamics and Fourier transform infrared spectroscopy.” Mater. Sci. Eng., C, 27(3), 352–371.
Black, J. (1992). Biological performance of materials: Fundamentals of biocompatibility, Marcel Dekker, New York.
Boskey, A. L. (2003). “Biomineralization: An overview.” Connect. Tissue Res., 44(1), 5–9.
Brooks, B. R., Bruccoleri, R. E., Olafson, B. D., States, D. J., Swaminathan, S., and Karplus, M. J. (1983). “CHARMM: A program for macromolecular energy, minimization, and dynamics calculations.” J. Comput. Chem., 4(2), 187–217.
Buehler, M. J. (2006a). “Atomistic and continuum modeling of mechanical properties of collagen: Elasticity, fracture, and self-assembly.” J. Mater. Res., 21(8), 1947–1961.
Buehler, M. J. (2006b). “Nature designs tough collagen: Explaining the nanostructure of collagen fibrils.” Proc. Natl. Acad. Sci. U.S.A., 103(33), 12285–12290.
Buehler, M. J. (2007). “Molecular nanomechanics of nascent bone: Fibrillar toughening by mineralization.” Nanotechnology, 18(29), 295102.
Currey, J. (1984). Mechanical adaptations of bones, Princeton University Press, Princeton, N.J.
Feller, S. E., Zhang, Y., Pastor, R. W., and Brooks, B. R. (1995). “Constant pressure molecular dynamics simulation: The Langevin piston method.” J. Chem. Phys., 103(11), 4613–4621.
Fitton-Jackson, S. (1957). “The fine structure of developing bone in the embryonic fowl.” Proc. R. Soc. London, Ser. B, 146, 270–280.
Fritsch, A., and Hellmich, C. (2007). “‘Universal’ microstructural patterns in cortical and trabecular, extracellular and extravascular bone materials: Micromechanics-based prediction of anisotropic elasticity.” J. Theor. Biol., 244(4), 597–620.
Ghosh, P., Katti, D. R., and Katti, K. S. (2006). “Impact of -sheet conformations on the mechanical response of protein in biocomposites.” Mater. Manuf. Processes, 21, 276–282.
Ghosh, P., Katti, D. R., and Katti, K. S. (2007). “Mineral proximity influences mechanical response of proteins in biological mineral-protein hybrid systems.” Biomacromolecules, 8, 851–856.
Grubmüller, H., Heymann, B., and Tavan, P. (1996). “Ligand binding: Molecular mechanics calculation of the streptavidin-biotin rupture force.” Science, 271(5251), 997–999.
Hellmich, C., Barthélémy, J.-F., and Dormieux, L. (2004a). “Mineral-collagen interactions in elasticity of bone ultrastructure—A continuum micromechanics approach.” Eur. J. Mech. A/Solids, 23(5), 783–810.
Hellmich, C., Ulm, F.-J., and Dormieux, L. (2004b). “Can the diverse elastic properties of trabecular and cortical bone be attributed to only a few tissue-independent phase properties and their interactions? Arguments from a multiscale approach.” Biomech. Model. Mechanobiol., 2(4), 219–238.
Humphrey, W., Dalke, A., and Schulten, K. (1996). “VMD: Visual molecular dynamics.” J. Mol. Graphics, 14(1), 33–38⟩.
Isralewitz, B., Izrailev, S., and Schulten, K. (1997). “Binding pathway of retinal to bacterio-opsin: A prediction by molecular dynamics simulations.” Biophys. J., 73(6), 2972–2979.
Izrailev, S., et al. (1998). “Steered molecular dynamics.” Computational molecular dynamics: Challenges, methods, ideas, Vol. 4 of Lecture Notes in Computational Science and Engineering, P. Deuflhard, J. Hermans, B. Leimkuhler, A. E. Mark, S. Reich, and R. D. Skeel, eds., Springer, Berlin, 39–65.
Izrailev, S., Stepaniants, S., Balsera, M., Oono, Y., and Schulten, K. (1997). “Molecular dynamics study of unbinding of the avidin-biotin complex.” Biophys. J., 72(4), 1568–1581.
Ji, B., and Gao, H. (2004). “Mechanical properties of nanostructure of biological materials.” J. Mech. Phys. Solids, 52(9), 1963–1990.
Ji, B., and Gao, H. (2006). “Elastic properties of nanocomposite structure of bone.” Compos. Sci. Technol., 66(9), 1212–1218.
Kadler, K. E., Holmes, D. F., Trotter, J. A., and Chapman, J. A. (1996). “Collagen fibril formation.” Biochem. J., 316, 1–11.
Kale, L., et al. (1999). “NAMD2: Greater scalability for parallel molecular dynamics.” J. Comput. Phys., 151(1), 283–312⟩.
Katti, D. R., Ghosh, P., Schmidt, S., and Katti, K. S. (2005a). “Mechanical properties of sodium montmorillonite interlayer intercalated with amino acids.” Biomacromolecules, 6(6), 3276–3282.
Katti, D. R., Schmidt, S., Ghosh, P., and Katti, K. S. (2005b). “Modeling response of pyrophyllite clay interlayer to applied stress using steered molecular dynamics.” Clays Clay Miner., 52(2), 171–178.
Katti, D. R., Schmidt, S. R., Ghosh, P., and Katti, K. S. (2007). “Molecular modeling of the mechanical behavior and interactions in dry and slightly hydrated sodium montmorillonite interlayer.” Can. Geotech. J., 44, 425–435.
Kosztin, D., Izrailev, S., and Schulten, K. (1999). “Unbinding of retinoic acid from its receptor studied by steered molecular dynamics.” Biophys. J., 76(1), 188–197.
Krammer, A., Lu, H., Isralewitz, B., Schulten, K., and Vogel, V. (1999). “Forced unfolding of the fibronectin type III module reveals a tensile molecular recognition switch.” Proc. Natl. Acad. Sci. U.S.A., 96(4), 1351–1356.
Landis, W. J. (1995). “The strength of a calcified tissue depends in part on the molecular structure and organization of its constituent mineral crystals in their organic matrix.” Bone (N.Y.), 16(5), 533–544.
Lu, H., Isralewitz, B., Krammer, A., Vogel, V., and Schulten, K. (1998). “Unfolding of titin immunoglobulin domains by steered molecular dynamics simulation.” Biophys. J., 75(2), 662–671.
Lu, H., Krammer, A., Isralewitz, B., Vogel, V., and Schulten, K. (2000). Elastic filaments of the cell, J. Pollack and H. Granzier, eds., Kluwer Academic/Plenum Publishers, New York.
Lu, H., and Schulten, K. (1999a). “Steered molecular dynamics simulation of conformational changes of immunoglobulin domain I27 interprete atomic force microscopy observations.” Chem. Phys., 247(1), 141–153.
Lu, H., and Schulten, K. (1999b). “Steered molecular dynamics simulations of force-induced protein domain unfolding.” Proteins: Struct., Funct., Genet., 35(4), 453–463.
Malone, J. P., George, A. and Veis, A. (2004). “Type I collagen N-telopeptides adopt an ordered structure when docked to their helix receptor during fibrillogenesis.” Proteins: Struct., Funct., Bioinf., 54(2), 206–215.
Marieb, E. N. (1998). Human anatomy and physiology, 4th Ed., Benjamin/Cummings Science Publishing, Menlo Park, Calif.
Martyna, G. J., Tobias, D. J., and Klein, M. L. (1994). “Constant pressure molecular dynamics algorithms.” J. Chem. Phys., 101(5), 4177–4189.
Molnar, F., Ben-Nun, M., Martínez, T. J., and Schulten, K. (2000). “Characterization of a conical intersection between the ground and first excited state for a retinal analog.” J. Mol. Struct.: THEOCHEM, 506(1–3), 169–178.
Murugan, R., and Ramakrishna, S. (2005). “Development of nanocomposites for bone grafting.” Compos. Sci. Technol., 65(15–16), 2385–2406.
Nylen, M. U., Scott, D. B., and Mosley, V. M. (1960). Calcification in biological systems, R. F. Songnnaes, ed., Am. Assoc. Adv. Sci., Washington, D.C., 129–142.
Ramakrishna, S., Mayer, J., Wintermantel, E., and Leong, W. K. (2001). “Biomedical applications of polymer-composite materials: A review.” Compos. Sci. Technol., 61(9), 1189–1224.
Reilly, D. T., Burstein, A. H., and Frankel, V. H. (1974). “The elastic modulus for bone.” J. Biomech., 7(3), 271–272.
Rho, J. Y., Tsui, T. Y., and Pharr, G. M. (1997). “Elastic properties of human cortical and trabecular lamellar bone measured by nanoindentation.” Biomaterials, 18(20), 1325–1330.
Schmidt, S., Katti, D., Ghosh, P., and Katti, K. (2005). “Evolution of mechanical response of sodium montmorillonite interlayer with increasing hydration.” Langmuir, 21, 8069–8076.
Schulten, K., Schulten, Z., and Szabo, A. (1981). “Dynamics of reactions involving diffusive barrier crossing.” J. Chem. Phys., 74(8), 4426–4432.
Sikdar, D., Katti, D. R., Katti, K. S., and Bhowmik, R. (2006). “Insight into molecular interactions between constituents in polymer clay nanocomposites.” Polymer, 47, 5196–5205.
Sudarsanan, K., and Young, R. A. (1969). “Significant precision in crystal structural details. Holly Springs hydroxyapatite.” Acta Crystallogr., Sect. B: Struct. Crystallogr. Cryst. Chem., 25, 1534–1543.
Tasker, P. W. (1979). “The stability of ionic crystal surfaces.” J. Phys. C, 12(22), 4977–84.
Tortora, G. J. (1989). Principles of human anatomy, 5th Ed., Harper and Row, New York.
Von Recum, A. F. (1998). Handbook of biomaterials evaluation, 2nd Ed., CRC, Boca Raton, Fla.
Weiner, S., and Wagner, H. D. (1998). “The material bone: Structure–mechanical function relations.” Annu. Rev. Mater. Res., 28, 271–298.
Wriggers, W., and Schulten, K. (1999). “Investigating a back door mechanism of actin phosphate release by steered molecular dynamics.” Proteins: Struct., Funct., Genet., 35(2), 262–273.
Ziv, V., and Weiner, S. (1994). “Bone crystal sizes: A comparison of transmission electron microscopic and X-ray diffraction line width broadening tecniques.” Connect. Tissue Res., 30(3), 165–175.
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Published In
Journal of Engineering Mechanics
Volume 135 • Issue 5 • May 2009
Pages: 413 - 421
Copyright
© 2009 ASCE.
History
Received: Jul 31, 2007
Accepted: Mar 18, 2008
Published online: May 1, 2009
Published in print: May 2009
Notes
Note. Associate Editor: Christian Hellmich
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