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Heterogeneous nanomechanical properties of type I collagen in longitudinal direction

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Abstract

Collagen is an abundant structural biopolymer in mammal vertebrates, providing structural support as well as mechanical integrity for connective tissues such as bone, ligament, and tendon. The mechanical behaviours of these tissues are determined by the nanomechanics of their structures at different hierarchies and the role of collagen structures in the extracellular matrix. Some studies revealed that there is significant microstructural difference in the longitudinal direction of the collagen fibril, which challenges the conventional rod-like assumption prevalently adopted in the existing studies. Motivated by this discrepancy, in this study, we investigated the longitudinal heterogeneous nanomechanical properties of type I collagen molecule to probe the origin of the longitudinal heterogeneity of the collagen fibril at the molecular level. A full length type I collagen molecule structure was built based on the experimentally calibrated nanostructure. Then, a suitable strain rate was determined for stretching the three intact ‘gap’ regions and three intact ‘overlap’ regions of the collagen molecule. Further, the nanomechanical properties of the six collagen molecule segments were characterized by performing steered molecular dynamics simulations, using the obtained suitable strain rate in modelling. The results indicate that this computational model can be used to capture the mechanical behaviour of the collagen molecule under physiological stress conditions. Moreover, the ‘gap’ regions show a lower stiffness and undergo a slightly lager strain in the unwinding process, compared to the ‘overlap’ regions of the collagen molecule. This investigation provides insights into the origin of the longitudinal heterogeneity of collagen fibrils at the molecular level and suggests that it is of significant importance to consider the longitudinal heterogeneous mechanical properties of the collagen molecule in the development of coarse-grained models of collagen-related tissues.

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References

  • Baldwin SJ, Quigley AS, Clegg C, Kreplak L (2014) Nanomechanical mapping of hydrated rat tail tendon collagen I fibrils. Biophys J 107:1794–1801

    Article  Google Scholar 

  • Balooch M, Habelitz S, Kinney J, Marshall S, Marshall G (2008) Mechanical properties of mineralized collagen fibrils as influenced by demineralization. J Struct Biol 162:404–410

    Article  Google Scholar 

  • Berendsen HJ, Postma JP, van Gunsteren WF, Hermans J (1981) Interaction models for water in relation to protein hydration. In: Pullman B (ed) Intermolecular forces. Springer, Berlin, pp 331–342

  • Berendsen HJ, van der Spoel D, van Drunen R (1995) GROMACS: a message-passing parallel molecular dynamics implementation. Comput Phys Commun 91:43–56

    Article  Google Scholar 

  • Bodian DL, Radmer RJ, Holbert S, Klein TE (2011) Molecular dynamics simulations of the full triple helical region of collagen type I provide an atomic scale view of the protein’s regional heterogeneity. In: Pacific symposium on biocomputing. pacific symposium on biocomputing, p. 193

  • Bozec L, Horton M (2005) Topography and mechanical properties of single molecules of type I collagen using atomic force microscopy. Biophys J 88:4223–4231

    Article  Google Scholar 

  • Buehler MJ (2006a) Atomistic and continuum modeling of mechanical properties of collagen: elasticity, fracture, and self-assembly. J Mater Res 21:1947–1961

    Article  Google Scholar 

  • Buehler MJ (2006b) Nature designs tough collagen: explaining the nanostructure of collagen fibrils. Proc Natl Acad Sci 103:12285–12290

    Article  Google Scholar 

  • Buehler MJ (2008) Nanomechanics of collagen fibrils under varying cross-link densities: atomistic and continuum studies. J Mech Behav Biomed Mater 1:59–67

    Article  Google Scholar 

  • Cusack S, Miller A (1979) Determination of the elastic constants of collagen by Brillouin light scattering. J Mol Biol 135:39–51

    Article  Google Scholar 

  • Depalle B, Qin Z, Shefelbine SJ, Buehler MJ (2014) Influence of cross-link structure, density and mechanical properties in the mesoscale deformation mechanisms of collagen fibrils. J Mech Behav Biomed Mater 52:1–13

    Article  Google Scholar 

  • Eppell S, Smith B, Kahn H, Ballarini R (2006) Nano measurements with micro-devices: mechanical properties of hydrated collagen fibrils. J R Soc Interface 3:117–121

    Article  Google Scholar 

  • Essmann U, Perera L, Berkowitz ML, Darden T, Lee H, Pedersen LG (1995) A smooth particle mesh Ewald method. J Chem Phys 103:8577–8593

    Article  Google Scholar 

  • Fratzl P, Misof K, Zizak I, Rapp G, Amenitsch H, Bernstorff S (1998) Fibrillar structure and mechanical properties of collagen. J Struct Biol 122:119–122

    Article  Google Scholar 

  • Gautieri A, Vesentini S, Montevecchi FM, Redaelli A (2008) Mechanical properties of physiological and pathological models of collagen peptides investigated via steered molecular dynamics simulations. J Biomech 41:3073–3077

    Article  Google Scholar 

  • Gautieri A, Buehler MJ, Redaelli A (2009a) Deformation rate controls elasticity and unfolding pathway of single tropocollagen molecules. J Mech Behav Biomed Mater 2:130–137

    Article  Google Scholar 

  • Gautieri A, Vesentini S, Redaelli A, Buehler MJ (2009b) Single molecule effects of osteogenesis imperfecta mutations in tropocollagen protein domains. Protein Sci 18:161–168

    Google Scholar 

  • Gautieri A, Russo A, Vesentini S, Redaelli A, Buehler MJ (2010) Coarse-grained model of collagen molecules using an extended MARTINI force field. J Chem Theory Comput 6:1210–1218

    Article  Google Scholar 

  • Gautieri A, Vesentini S, Redaelli A, Buehler MJ (2011) Hierarchical structure and nanomechanics of collagen microfibrils from the atomistic scale up. Nano Lett 11:757–766

    Article  Google Scholar 

  • Gautieri A, Vesentini S, Redaelli A, Buehler MJ (2012a) Viscoelastic properties of model segments of collagen molecules. Matrix Biol 31:141–149

    Article  Google Scholar 

  • Gautieri A, Vesentini S, Redaelli A, Buehler MJ (2012b) Osteogenesis imperfecta mutations lead to local tropocollagen unfolding and disruption of H-bond network. RSC Adv 2:3890–3896

    Article  Google Scholar 

  • Gautieri A, Vesentini S, Redaelli A, Ballarini R (2013) Modeling and measuring visco-elastic properties: from collagen molecules to collagen fibrils. Int J Non-Linear Mech 56:25–33

    Article  Google Scholar 

  • Gentleman E, Lay AN, Dickerson DA, Nauman EA, Livesay GA, Dee KC (2003) Mechanical characterization of collagen fibers and scaffolds for tissue engineering. Biomaterials 24:3805–3813

    Article  Google Scholar 

  • Gopalakrishnan R, Singam EA, Sundar JV, Subramanian V (2015) Interaction of collagen like peptides with gold nanosurfaces: a molecular dynamics investigation. Phys Chem Chem Phys 17:5172–5186

    Article  Google Scholar 

  • Graham JS, Vomund AN, Phillips CL, Grandbois M (2004) Structural changes in human type I collagen fibrils investigated by force spectroscopy. Exp Cell Res 299:335–342

    Article  Google Scholar 

  • Gupta H, Messmer P, Roschger P, Bernstorff S, Klaushofer K, Fratzl P (2004) Synchrotron diffraction study of deformation mechanisms in mineralized tendon. Phys Rev Lett 93:158101

    Article  Google Scholar 

  • Harley R, James D, Miller A, White J (1977) Phonons and the elastic moduli of collagen and muscle. Nat 267:285–287. doi:10.1038/267285a0

  • Heim AJ, Matthews WG, Koob TJ (2006) Determination of the elastic modulus of native collagen fibrils via radial indentation. Appl Phys Lett 89:181902

    Article  Google Scholar 

  • Hess B, Bekker H, Berendsen HJ, Fraaije JG (1997) LINCS: a linear constraint solver for molecular simulations. J Comput Chem 18:1463–1472

    Article  Google Scholar 

  • Hodge AJ, Schmitt FO (1960) The charge profile of the tropocollagen macromolecule and the packing arrangement in native-type collagen fibrils. Proc Natl Acad Sci USA 46:186

    Article  Google Scholar 

  • Hofmann H, Voss T, Kühn K, Engel J (1984) Localization of flexible sites in thread-like molecules from electron micrographs: comparison of interstitial, basement membrane and intima collagens. J Mol Biol 172:325–343

    Article  Google Scholar 

  • Hulmes D (2008) Collagen diversity, synthesis and assembly. In: Fratzl P (ed) Collagen. Springer, Berlin, pp 15–47

  • Husar-Memmer E, Ekici A, Al Kaissi A, Sticht H, Manger B, Schett G et al (2013) Premature osteoarthritis as presenting sign of type II collagenopathy: a case report and literature review. In: Seminars in arthritis and rheumatism, pp 355–360

  • Jenkins CL, Raines RT (2002) Insights on the conformational stability of collagen. Nat Prod Rep 19:49–59

    Article  Google Scholar 

  • Kadler KE, Baldock C, Bella J, Boot-Handford RP (2007) Collagens at a glance. J Cell Sci 120:1955–1958

    Article  Google Scholar 

  • Kim J-H, Lee G, Won Y, Lee M, Kwak J-S, Chun C-H et al (2015) Matrix cross-linking-mediated mechanotransduction promotes posttraumatic osteoarthritis. Proc Natl Acad Sci 112:9424–9429

    Article  Google Scholar 

  • Leistritz DF, Pepin MG, Schwarze U, Byers PH (2011) COL3A1 haploinsufficiency results in a variety of Ehlers–Danlos syndrome type IV with delayed onset of complications and longer life expectancy. Genet Med 13:717–722

    Article  Google Scholar 

  • Lindahl K, Åström E, Rubin C-J, Grigelioniene G, Malmgren B, Ljunggren Ö et al (2015) Genetic epidemiology, prevalence, and genotype-phenotype correlations in the Swedish population with osteogenesis imperfecta. Eur J Hum Genet 23:1042–1050

    Article  Google Scholar 

  • Lorenzo AC, Caffarena ER (2005) Elastic properties, Young’s modulus determination and structural stability of the tropocollagen molecule: a computational study by steered molecular dynamics. J Biomech 38:1527–1533

    Article  Google Scholar 

  • Maupetit J, Gautier R, Tufféry P (2006) SABBAC: online Structural Alphabet-based protein BackBone reconstruction from Alpha-Carbon trace. Nucleic Acids Res 34:W147–W151

    Article  Google Scholar 

  • Minary-Jolandan M, Yu M-F (2009) Nanomechanical heterogeneity in the gap and overlap regions of type I collagen fibrils with implications for bone heterogeneity. Biomacromolecules 10:2565–2570

    Article  Google Scholar 

  • Orgel JP, Irving TC, Miller A, Wess TJ (2006) Microfibrillar structure of type I collagen in situ. Proc Natl Acad Sci 103:9001–9005

    Article  Google Scholar 

  • Orgel JP, Persikov AV, Antipova O (2014) Variation in the helical structure of native collagen. PloS ONE 9:e89519

    Article  Google Scholar 

  • Parrinello M, Rahman A (1981) Polymorphic transitions in single crystals: a new molecular dynamics method. J Appl Phys 52:7182–7190

    Article  Google Scholar 

  • Pradhan SM, Katti DR, Katti KS (2011) Steered molecular dynamics study of mechanical response of full length and short collagen molecules. J Nanomech Micromech 1:104–110

    Article  Google Scholar 

  • Ravikumar K, Humphrey J, Hwang W (2007) Spontaneous unwinding of a labile domain in a collagen triple helix. J Mech Mater Struct 2:999–1010

    Article  Google Scholar 

  • Robin NH, Moran RT, Ala-Kokko L (2014) Stickler syndrome In: Pagon RA, Adam MP, Ardinger HH et al (eds) GeneReviews(r) [Internet], 1993–2016. University of Washington, Seattle. http://www.ncbi.nlm.nih.gov/books/NBK1302/

  • Robinson R, Watson M (1952) Collagen–crystal relationships in bone as seen in the electron microscope. Anat Rec 114:383–409

    Article  Google Scholar 

  • Sasaki N, Odajima S (1996) Elongation mechanism of collagen fibrils and force–strain relations of tendon at each level of structural hierarchy. J Biomech 29:1131–1136

    Article  Google Scholar 

  • Shen ZL, Dodge MR, Kahn H, Ballarini R, Eppell SJ (2008) Stress–strain experiments on individual collagen fibrils. Biophys J 95:3956–3963

    Article  Google Scholar 

  • Sherman VR, Yang W, Meyers MA (2015) The materials science of collagen. J Mech Behav Biomed Mater 52:22–50

    Article  Google Scholar 

  • Spitzner E-C, Röper S, Zerson M, Bernstein A, Magerle R (2015) Nanoscale swelling heterogeneities in type I collagen fibrils. ACS Nano 9:5683–5694

    Article  Google Scholar 

  • Stevens MJ (2008) Simulation of the mechanical strength of a single collagen molecule. Biophys J 95:33–39

    Article  Google Scholar 

  • Streeter I, de Leeuw NH (2011) A molecular dynamics study of the interprotein interactions in collagen fibrils. Soft Matter 7:3373–3382

    Article  Google Scholar 

  • Sun Y-L, Luo Z-P, Fertala A, An K-N (2002) Direct quantification of the flexibility of type I collagen monomer. Biochem Biophys Res Commun 295:382–386

    Article  Google Scholar 

  • Sun Y-L, Luo Z-P, Fertala A, An K-N (2004) Stretching type II collagen with optical tweezers. J Biomech 37:1665–1669

    Article  Google Scholar 

  • Uzel SG, Buehler MJ (2009) Nanomechanical sequencing of collagen: tropocollagen features heterogeneous elastic properties at the nanoscale. Integr Biol 1:452–459

    Article  Google Scholar 

  • van der Rijt JA, van der Werf KO, Bennink ML, Dijkstra PJ, Feijen J (2006) Micromechanical testing of individual collagen fibrils. Macromol Biosci 6:697–702

    Article  Google Scholar 

  • Vesentini S, Fitié CF, Montevecchi FM, Redaelli A (2005) Molecular assessment of the elastic properties of collagen-like homotrimer sequences. Biomech Model Mechanobiol 3:224–234

    Article  Google Scholar 

  • Vesentini S, Redaelli A, Gautieri A (2013) Nanomechanics of collagen microfibrils. Muscles Ligaments Tendons J 3:23

    Google Scholar 

  • Weiner S, Wagner HD (1998) The material bone: structure-mechanical function relations. Annu Rev Mater Sci 28:271–298

    Article  Google Scholar 

  • Wenger MP, Bozec L, Horton MA, Mesquida P (2007) Mechanical properties of collagen fibrils. Biophys J 93:1255–1263

    Article  Google Scholar 

  • Wenger MP, Mesquida P (2011) Longitudinal variations in the Poisson’s ratio of collagen fibrils. Appl Phys Lett 98:163707

    Article  Google Scholar 

  • Yang W, Sherman VR, Gludovatz B, Schaible E, Stewart P, Ritchie RO et al (2015) On the tear resistance of skin. Nat Commun 6

  • Zhou Z, Minary-Jolandan M, Qian D (2015) A simulation study on the significant nanomechanical heterogeneous properties of collagen. Biomech Model Mechanobiol 14(3): 445–457

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Acknowledgements

The authors thank Joseph Orgel (Center For Molecular Study Of Condensed Soft Matter, Pritzker Institute of Biomedical Science and Engineering at the Illinois Institute of Technology and Argonne National Lab, USA) for his help on dividing the gap and overlap regions of the collagen molecule. This research was funded by ARC Discovery Project (DP150100828). The High Performance Computer resources provided by Queensland University of Technology (QUT) are gratefully acknowledged. Also the financial support of China Scholarship Council (CSC) scholarship from Chinese government and Top-up scholarship from QUT are greatly appreciated.

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Authors and Affiliations

  1. School of Chemistry Physics and Mechanical Engineering, Queensland University of Technology, Brisbane, Australia

    Ming Tang & YuanTong Gu

  2. Centre for Composite Material, University of Delaware, Newark, DE, 19711, USA

    Tong Li

  3. School of Mathematical Sciences, Queensland University of Technology, Brisbane, 4001, Australia

    Neha S. Gandhi & Kevin Burrage

  4. ARC Centre of Excellence for Mathematical and Statistical Frontiers, Queensland University of Technology, Brisbane, 4001, Australia

    Kevin Burrage

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  1. Ming Tang
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Tang, M., Li, T., Gandhi, N.S. et al. Heterogeneous nanomechanical properties of type I collagen in longitudinal direction. Biomech Model Mechanobiol 16, 1023–1033 (2017). https://doi.org/10.1007/s10237-016-0870-6

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