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Radial variations in mechanical behaviour and fibrillar structure in annulus fibrosus has foundations at molecular length-scale: Insights from molecular dynamics simulations of type I and type II collagen molecules

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Abstract

In annulus fibrosus (AF), type I collagen (Col-I) dominates outer AF (OAF) while type II collagen (Col-II) dominates inner AF (IAF). Using molecular dynamics simulations, this work reports how molecular-level structural and mechanical differences between Col-I and Col-II contribute to AF exhibiting radially varying structure and mechanical properties. Results show that differences in interpolypeptide forces and residue solvent accessibility contributes to Col-I showing intact triple-helix, lower backbone kinks and interpolypeptide separation (IPS), and thus contributing to expression of lower intermolecular spacing in collagen fibrils, lower lamellae thickness and lower water content in OAF. Furthermore, Col-I primarily exhibits backbone stretch while Col-II exhibit backbone straightening under tension, despite having comparable elastic moduli of ~ 3.5 GPa and ~ 3.2 GPa during backbone stretch. Such differences contribute to OAF showing stiffer stress–strain characteristics under tension. Furthermore, higher slenderness ratio of Col-I leads to buckling under compression—contributing to larger radial bulge being exhibited by OAF lamellae.

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References

  1. J.J. Cassidy, A. Hiltner, E. Baer, Hierarchical structure of the intervertebral disc. Connect. Tissue Res. 23(1), 75 (1989)

    Article  CAS  Google Scholar 

  2. G.A. Holzapfel, C.A.J. Schulze-Bauer, G. Feigl, P. Regitnig, Single lamellar mechanics of the human lumbar anulus fibrosus. Biomech. Model. Mechanobiol. 3(3), 125 (2005)

    Article  CAS  Google Scholar 

  3. F. Marchand and A. M. Ahmed: Spine (Phila. Pa. 1976). 15, 402 (1990).

  4. P. Adams, D.R. Eyre, H. Muir, Biochemical aspects of development and ageing of human lumbar intervertebral discs. Rheumatology 16(1), 22 (1977)

    Article  CAS  Google Scholar 

  5. G. Schollmeier, R. Lahr-Eigen, K.U. Lewandrowski, Observations on fiber-forming collagens in the anulus fibrosus. Spine (Phila. Pa. 1976) 25(21), 2736 (2000)

    Article  CAS  Google Scholar 

  6. J. Antoniou, T. Steffen, F. Nelson, N. Winterbottom, A.P. Hollander, R.A. Poole, M. Aebi, M. Alini, The human lumbar intervertebral disc: Evidence for changes in the biosynthesis and denaturation of the extracellular matrix with growth, maturation, ageing, and degeneration. J. Clin. Invest. 98(4), 996–1003 (1996)

    Article  CAS  Google Scholar 

  7. K. Gelse, E. Pöschl, T. Aigner, Collagens—Structure, function, and biosynthesis. Adv. Drug Deliv. Rev. 55(12), 1531 (2003)

    Article  CAS  Google Scholar 

  8. P. Bruckner, M. van der Rest, Structure and function of cartilage collagens. Microsc. Res. Tech. 28(5), 378–84 (1994)

    Article  CAS  Google Scholar 

  9. Y.L. Sun, Z.P. Luo, A. Fertala, K.N. An, Direct quantification of the flexibility of type I collagen monomer. Biochem. Biophys. Res. Commun. 295(2), 382 (2002)

    Article  CAS  Google Scholar 

  10. Y.L. Sun, Z.P. Luo, A. Fertala, K.N. An, Stretching type II collagen with optical tweezers. J. Biomech. 37(11), 1665 (2004)

    Article  Google Scholar 

  11. R. Harley, D. James, A. Miller, J.W. White, Phonons and the elastic moduli of collagen and muscle [38]. Nature 267(5608), 285 (1977)

    Article  CAS  Google Scholar 

  12. S. Cusack, A. Miller, Determination of the elastic constants of collagen by Brillouin light scattering. J. Mol. Biol. 135(1), 39 (1979)

    Article  CAS  Google Scholar 

  13. H. Hofmann, T. Voss, K. Kühn, J. Engel, Localization of flexible sites in thread-like molecules from electron micrographs. Comparison of interstitial, basement membrane and intima collagens. J. Mol. Biol. 172(3), 325 (1984)

    Article  CAS  Google Scholar 

  14. N. Sasaki, S. Odajima, Elongation mechanism of collagen fibrils and force-strain relations of tendon at each level of structural hierarchy. J. Biomech. 29(9), 1131 (1996)

    Article  CAS  Google Scholar 

  15. M.J. Buehler, Atomistic and continuum modeling of mechanical properties of collagen: Elasticity, fracture, and self-assembly. J. Mater. Res. 21(8), 1947 (2006)

    Article  CAS  Google Scholar 

  16. A. Gautieri, M.J. Buehler, A. Redaelli, Deformation rate controls elasticity and unfolding pathway of single tropocollagen molecules. J. Mech. Behav. Biomed. Mater. 2(2), 130 (2009)

    Article  Google Scholar 

  17. D.K. Dubey, V. Tomar, Role of the nanoscale interfacial arrangement in mechanical strength of tropocollagen-hydroxyapatite-based hard biomaterials. Acta Biomater. 5(7), 2704 (2009)

    Article  CAS  Google Scholar 

  18. M. Tang, T. Li, N.S. Gandhi, K. Burrage, Y.T. Gu, Heterogeneous nanomechanical properties of type I collagen in longitudinal direction. Biomech. Model. Mechanobiol. 16(3), 1023 (2017)

    Article  Google Scholar 

  19. M. Tang, T. Li, E. Pickering, N.S. Gandhi, K. Burrage, Y.T. Gu, Steered molecular dynamics characterization of the elastic modulus and deformation mechanisms of single natural tropocollagen molecules. J. Mech. Behav. Biomed. Mater. 86, 359 (2018)

    Article  CAS  Google Scholar 

  20. J.E. Scott, M. Haigh, Proteoglycan-collagen interactions in intervertebral disc. A chondroitin sulphate proteoglycan associates with collagen fibrils in rabbit annulus fibrosus at the d-e bands. Biosci. Rep. 6(10), 879 (1986)

    Article  CAS  Google Scholar 

  21. M.D. Grynpas, D.R. Eyre, D.A. Kirschner, Collagen type II differs from type I in native molecular packing. BBA - Protein Struct. 626(2), 346 (1980)

    Article  CAS  Google Scholar 

  22. S. Ebara, J.C. Iatridis, L.A. Setton, R.J. Foster, C. Van Mow, M. Weidenbaum, Tensile properties of nondegenerate human lumbar anulus fibrosus. Spine (Phila. Pa. 1976) 21(4), 452 (1996)

    Article  CAS  Google Scholar 

  23. D.L. Skaggs, M. Weidenbaum, J.C. Latridis, A. Ratcliffe, V.C. Mow, Spine (Phila. Pa. 1976) 19, 1310 (1994)

    Article  CAS  Google Scholar 

  24. W.M. Han, N.L. Nerurkar, L.J. Smith, N.T. Jacobs, R.L. Mauck, D.M. Elliott, Multi-scale structural and tensile mechanical response of annulus fibrosus to osmotic loading. Ann. Biomed. Eng. 40(7), 1610 (2012)

    Article  Google Scholar 

  25. C.A. Miles, T.J. Sims, N.P. Camacho, A.J. Bailey, The role of the α2 chain in the stabilization of the collagen type I heterotrimer: A study of the type I homotrimer in oim mouse tissues. J. Mol. Biol. 321(5), 797–805 (2002)

    Article  CAS  Google Scholar 

  26. J.C. Iatridis, J.J. MacLean, M. O’Brien, I.A.F. Stokes, Measurements of proteoglycan and water content distribution in human lumbar intervertebral discs. Spine (Phila. Pa. 1976) 32(14), 1493 (2007)

    Article  Google Scholar 

  27. J.P.G. Urban, S. Roberts, Mol. Med. Today 1, 329 (1995)

    Article  CAS  Google Scholar 

  28. S.M. Pradhan, D.R. Katti, K.S. Katti, Steered molecular dynamics study of mechanical response of full length and short collagen molecules. J. Nanomech. Micromech. 1(3), 104 (2011)

    Article  Google Scholar 

  29. S.M. Pradhan, K.S. Katti, D.R. Katti, Structural hierarchy controls deformation behavior of collagen. Biomacromolecules (2012). https://doi.org/10.1021/bm300801a

    Article  Google Scholar 

  30. A.C. Lorenzo, E.R. Caffarena, Elastic properties, Young’s modulus determination and structural stability of the tropocollagen molecule: A computational study by steered molecular dynamics. J. Biomech. 38(7), 1527 (2005)

    Article  Google Scholar 

  31. S. Vesentini, C.F.C. Fitié, F.M. Montevecchi, A. Redaelli, Molecular assessment of the elastic properties of collagen-like homotrimer sequences. Biomech. Model. Mechanobiol. 3(4), 224 (2005)

    Article  CAS  Google Scholar 

  32. S. Varma, J.P.R.O. Orgel, J.D. Schieber, Nanomechanics of Type I Collagen. Biophys. J. 111(1), 50 (2016)

    Article  CAS  Google Scholar 

  33. G.D. O’Connell, S. Sen, D.M. Elliott, Human annulus fibrosus material properties from biaxial testing and constitutive modeling are altered with degeneration. Biomech. Model. Mechanobiol. 11(3–4), 493 (2012)

    Article  Google Scholar 

  34. G.D. O’Connell, W. Johannessen, E.J. Vresilovic, D.M. Elliott, Human internal disc strains in axial compression measured noninvasively using magnetic resonance imaging. Spine (Phila. Pa. 1976) 32, 2860–2868 (2007)

    Article  Google Scholar 

  35. G.D. O’Connell, E.J. Vresilovic, D.M. Elliott, Human intervertebral disc internal strain in compression: The effect of disc region, loading position, and degeneration. J. Orthop. Res. 29(4), 547–55 (2011)

    Article  Google Scholar 

  36. M. Mengoni, O. Kayode, S.N.F. Sikora, F.Y. Zapata-Cornelio, D.E. Gregory, R.K. Wilcox, Annulus fibrosus functional extrafibrillar and fibrous mechanical behaviour: Experimental and computational characterisation. R. Soc. Open Sci. (2017). https://doi.org/10.1098/rsos.170807

    Article  Google Scholar 

  37. B. Berg-Johansen, A.J. Fields, E.C. Liebenberg, A. Li, J.C. Lotz, Structure–function relationships at the human spinal disc-vertebra interface. J. Orthop. Res. 36(1), 192 (2018)

    Google Scholar 

  38. S. Demers, A.H. Bouzid, S. Nadeau, Effect of Sharpey’s fibers on the stress distribution in the anulus fibrosus of an intervertebral disc subjected to compression. Int. Rev. Model. Simul. 9(6), 414 (2016)

    Google Scholar 

  39. S. Brown, S. Rodrigues, C. Sharp, K. Wade, N. Broom, I.W. McCall, S. Roberts, Staying connected: Structural integration at the intervertebral disc–vertebra interface of human lumbar spines. Eur. Spine J. 26(1), 248 (2017)

    Article  Google Scholar 

  40. N. Sasaki, S. Odajima, Stress–strain curve and Young’s modulus of a collagen molecule as determined by the X-ray diffraction technique. J. Biomech. 29(5), 655 (1996)

    Article  CAS  Google Scholar 

  41. M.A. Soltz, G.A. Ateshian, A conewise linear elasticity mixture model for the analysis of tension-compression nonlinearity in articular cartilage. J. Biomech. Eng. 122(6), 576–86 (2000)

    Article  CAS  Google Scholar 

  42. M. Mohammadkhah, P. Murphy, C.K. Simms, Collagen fibril organization in chicken and porcine skeletal muscle perimysium under applied tension and compression. J. Mech. Behav. Biomed. Mater. 77, 734–744 (2018)

    Article  CAS  Google Scholar 

  43. J. Dvorak, M.M. Panjabi, J.E. Novotny, J.A. Antinnes, In vivo flexion/extension of the normal cervical spine. J. Orthop. Res. 9(6), 828 (1991)

    Article  CAS  Google Scholar 

  44. M. Panjabi, A.A. White, A mathematical approach for three-dimensional analysis of the mechanics of the spine. J. Biomech. 4(3), 203 (1971)

    Article  CAS  Google Scholar 

  45. M.M. Panjabi, T.R. Oxland, I. Yamamoto, J.J. Crisco, Mechanical behavior of the human lumbar and lumbosacral spine as shown by three-dimensional load-displacement curves. J. Bone Jt. Surg. Ser. A 76(3), 413 (1994)

    Article  CAS  Google Scholar 

  46. M.J. Buehler, S.Y. Wong, Entropic elasticity controls nanomechanics of single tropocollagen molecules. Biophys. J. 93(1), 37 (2007)

    Article  CAS  Google Scholar 

  47. S. Ahmed, T. Hassan, A. Hanif, Effects of lumbar stabilization exercise in management of pain and restoration of function in patients with postero lateral disc herniation. Ann. Vol. Apr.–Jun. (2012). https://doi.org/10.21649/akemu.v18i2.393

    Article  Google Scholar 

  48. M.A. Adams, B.J.C. Freeman, H.P. Morrison, I.W. Nelson, P. Dolan, Mechanical initiation of intervertebral disc degeneration. Spine (Phila. Pa. 1976) 25(13), 1625 (2000)

    Article  CAS  Google Scholar 

  49. S. Bhattacharya, D.K. Dubey, Effect of aggrecan degradation on the nanomechanics of hyaluronan in extra-fibrillar matrix of annulus fibrosus: A molecular dynamics investigation. J. Mech. Behav. Biomed. Mater. (2020). https://doi.org/10.1016/j.jmbbm.2020.103752

    Article  Google Scholar 

  50. C.C. Huang, G.S. Couch, E.F. Pettersen, T.E. Ferrin, A.E. Howard, T.E. Klein, in Pac. Symp. Biocomput. (1998), pp. 349–361

  51. D.L. Bodian, R.J. Radmer, S. Holbert, T.E. Klein, in Pacific Symp. Biocomput. 2011, PSB 2011 (2011), pp. 193–204

  52. J.P.R.O. Orgel, A. Miller, T.C. Irving, R.F. Fischetti, A.P. Hammersley, T.J. Wess, The in situ supermolecular structure of type I collagen. Structure 9(11), 1061 (2001)

    Article  CAS  Google Scholar 

  53. The UniProt Consortium: UniProt: A worldwide hub of protein knowledge The UniProt Consortium. Nucleic Acids Res. (2019)

  54. J.P.G. Urban, S. Roberts, Development and degeneration of the intervertebral discs. Mol. Med. Today 1(7), 329 (1995)

    Article  CAS  Google Scholar 

  55. J.E. Scott, T.R. Bosworth, A.M. Cribb, J.R. Taylor, The chemical morphology of age-related changes in human intervertebral disc glycosaminoglycans from cervical, thoracic and lumbar nucleus pulposus and annulus fibrosus. J. Anat. 184(Pt 1), 73 (1994)

    Google Scholar 

  56. W. Humphrey, A. Dalke, K. Schulten, VMD: Visual molecular dynamics. J. Mol. Graph. 14(1), 33 (1996)

    Article  CAS  Google Scholar 

  57. V. Makarov, B.M. Pettitt, M. Feig, Solvation and hydration of proteins and nucleic acids: A theoretical view of simulation and experiment. Acc. Chem. Res. 35(6), 376 (2002)

    Article  CAS  Google Scholar 

  58. S. Plimpton, Fast parallel algorithms for short-range molecular dynamics. J. Comput. Phys. 117(1), 1 (1995)

    Article  CAS  Google Scholar 

  59. B.R. Brooks, R.E. Bruccoleri, B.D. Olafson, D.J. States, S. Swaminathan, M. Karplus, CHARMM: A program for macromolecular energy, minimization, and dynamics calculations. J. Comput. Chem. 4(2), 187 (1983)

    Article  CAS  Google Scholar 

  60. M. Patel, D.K. Dubey, S.P. Singh, Phenomenological models of Bombyx mori silk fibroin and their mechanical behavior using molecular dynamics simulations. Mater. Sci. Eng. C (2020). https://doi.org/10.1016/j.msec.2019.110414

    Article  Google Scholar 

  61. A. Gautieri, M.I. Pate, S. Vesentini, A. Redaelli, M.J. Buehler, Hydration and distance dependence of intermolecular shearing between collagen molecules in a model microfibril. J. Biomech. 45(12), 2079 (2012)

    Article  Google Scholar 

  62. P.J. In’t Veld, M.J. Stevens, Simulation of the mechanical strength of a single collagen molecule. Biophys. J. 95(1), 33 (2008)

    Article  CAS  Google Scholar 

  63. P. Mark, L. Nilsson, Structure and dynamics of the TIP3P, SPC, and SPC/E water models at 298 K. J. Phys. Chem. A (2001). https://doi.org/10.1021/jp003020w

    Article  Google Scholar 

  64. P. Florová, P. Sklenovský, P. Banáš, M. Otyepka, Explicit water models affect the specific solvation and dynamics of unfolded peptides while the conformational behavior and flexibility of folded peptides remain intact. J. Chem. Theory Comput. (2010). https://doi.org/10.1021/ct1003687

  65. A.P. Thompson, S.J. Plimpton, W. Mattson, General formulation of pressure and stress tensor for arbitrary many-body interaction potentials under periodic boundary conditions. J. Chem. Phys. 131(15), 15410 (2009)

    Article  CAS  Google Scholar 

  66. M. Zhou, A new look at the atomic level virial stress: On continuum-molecular system equivalence. Proc. R. oc. A Math. Phys. Eng. Sci. 459(2037), 2347 (2003)

    Article  CAS  Google Scholar 

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  1. Department of Mechanical Engineering, Indian Institute of Technology Delhi, Haus Khas, New Delhi, 110016, India

    Shambo Bhattacharya & Devendra K. Dubey

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Bhattacharya, S., Dubey, D.K. Radial variations in mechanical behaviour and fibrillar structure in annulus fibrosus has foundations at molecular length-scale: Insights from molecular dynamics simulations of type I and type II collagen molecules. Journal of Materials Research 36, 3407–3425 (2021). https://doi.org/10.1557/s43578-021-00376-2

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