Abstract
Mechanics of collagen bio-structures at different scales (nano, micro, and macro) is addressed, aiming to describe multiscale mechanisms affecting the constitutive response of soft collagen-rich tissues. Single-scale elastic models of collagen molecules, fibrils, and crimped fibers are presented and integrated by means of consistent inter-scale relationships and homogenization arguments. In this way, a unique modeling framework based on a structural multiscale approach is obtained, which allows to analyze the macroscale mechanical behavior of soft collagenous tissues. It accounts for the dominant mechanisms at lower scales without introducing phenomenological descriptions. Comparisons between numerical results obtained via present model and the available experimental data in the case of tendons and aortic walls prove present multiscale approach to be effective in capturing the deep link between histology and mechanics, opening to the possibility of developing patient-specific diagnostic and clinical tools.
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The persistence length is the maximum contour length over which the corresponding molecular segment appears as straight under thermal fluctuations.
References
van Holde, K.E., Matthews, C.: Biochemistry. Benjamin/Cummings Publishing Company Inc., Menlo Park (1995)
Fratzl, P.: Collagen: Structure and Mechanics. Springer, New York (2008)
Bruel, A., Oxlund, H.: Changes in biomechanical properties, composition of collagen and elastin, and advanced glycation endproducts of the rat aorta in relation to age. Atherosclerosis 127, 155–165 (1996)
Bruel, A., Ørtoft, G., Oxlund, H.: Inhibition of cross-links in collagen is associated with reduced stiffness of the aorta in young rats. Atherosclerosis 140, 135–145 (1998)
Mao, J.R., Bristow, J.: The Ehlers–Danlos syndrome: on beyond collagens. J. Clin. Invest. 107, 1063–1069 (2001)
Carmo, M., Colombo, L., Bruno, A., Corsi, F.R.M., Roncoroni, L., Cuttin, M.S., Radice, F., Mussini, E., Settembrini, P.G.: Alteration of elastin, collagen and their cross-links in abdominal aortic aneurysms. Eur. J. Vasc. Endovasc. Surg. 23, 543–549 (2002)
Järvinen, T.A.H., Järvinen, T.L.N., Kannus, P., Józsa, L., Järvinen, M.: Collagen fibres of the spontaneously ruptured human tendons display decreased thickness and crimp angle. J. Orthop. Res. 22, 1303–1309 (2004)
Maceri, F., Marino, M., Vairo, G.: A unified multiscale mechanical model for soft collagenous tissues with regular fiber arrangement. J. Biomech. 43, 355–363 (2010)
Buehler, M.J., Wong, S.Y.: Entropic elasticity controls nanomechanics of single tropocollagen molecules. Biophys. J. 93, 37–43 (2007)
Marko, J.F., Siggia, E.D.: Stretching DNA. Macromolecules 28, 8759–8770 (1995)
MacKintosh, F.C., Käs, J., Janmey, P.A.: Elasticity of semiflexible biopolymer networks. Phys. Rev. Lett. 75, 4425–4428 (1995)
Sun, Y.L., Luo, Z.P., Fertala, A., An, K.N.: Direct quantification of the flexibility of type I collagen monomer. Biochem. Biophys. Res. Commun. 295, 382–386 (2002)
Wang, M.D., Yin, H., Landick, R., Gelles, J., Block, S.M.: Stretching DNA with optical tweezers. Biophys. J. 72, 1335–1346 (1997)
Holzapfel, G.A., Ogden, R.W.: On the bending and stretching elasticity of biopolymer filaments. J. Elast. 104, 319–342 (2010)
Maceri, F., Marino, M., Vairo, G.: Elasto-damage modeling of biopolymer molecules response. Comput. Model. Eng. Sci. (2012, to appear) ISSN: 1526-1492
Gautieri, A., Buehler, M.J., Redaelli, A.: Deformation rate controls elasticity and unfolding pathway of single tropocollagen molecules. J. Mech. Behav. Biomed. Mat. 2, 130–137 (2009)
Eyre, D.R., Weis, M.A., Wu, J.J.: Advances in collagen cross-link analysis. Methods 45(1), 65–74 (2008)
Orgel, J.P.R.O., Irving, T.C., Miller, A., Wess, T.J.: Microfibrillar structure of type I collagen in situ. Proc. Nat. Acad. Sci. USA 103, 9001–9005 (2006)
Petruska, J.A., Hodge, A.J.: A subunit model for the tropocollagen macromolecule. Proc. Natl Acad. Sci. USA 51, 871–876 (1964)
Pins, G.D., Christiansen, D.L., Patel, R., Silver, F.H.: Self-assembly of collagen fibers. Influence of fibrillar alignment and decorin on mechanical properties. Biophys. J. 73, 2164–2172 (1997)
Redaelli, A., Vesentini, S., Soncini, M., Vena, P., Mantero, S., Montevecchi, F.M.: Possible role of decorin glycosaminoglycans in fibril to fibril force transfer in relative mature tendons—a computational study from molecular to microstructural level. J. Biomech. 36, 1555–1569 (2003)
Craig, A.S., Birtles, M.J., Conway, J.F., Parry, D.A.: An estimate of the mean length of collagen fibrils in rat tail-tendon as a function of age. Connect. Tissue Res. 19, 51–62 (1989)
Provenzano, P.P., Vanderby, R.J.: Collagen fibril morphology and organization: implications for force transmission in ligament and tendon. Matrix Biol. 25, 71–84 (2006)
Fessel, G., Snedeker, J.G.: Equivalent stiffness after glycosaminoglycan depletion in tendon—an ultra-structural finite element model and corresponding experiments. J. Theor. Biol. 268, 77–83 (2011)
Martini, F.H., Timmons, M.J., Tallitsch, R.B.: Human Anatomy. Prentice Hall, Englewood Cliffs (1994)
Sasaki, N., Odajima, S.: Elongation mechanism of collagen fibrils and force–strain relations of tendon at each level of structural hierarchy. J. Biomech. 29, 1131–1136 (1996)
Hansen, K.A., Weiss, J.A., Barton, J.K.: Recruitment of tendon crimp with applied tensile strain. J. Biomech. Eng. 124, 72–77 (2002)
Yamamoto, E., Kogawa, D., Tokura, S., Hayashi, K.: Biomechanical response of collagen fascicles to restressing after stress deprivation during culture. J. Biomech. 40, 2063–2070 (2007)
Kannus, P.: Structure of the tendon connective tissue. Scand. J. Med. Sci. Sports 10, 312–320 (2000)
Silver, F.H., Freeman, J.W., Horvath, I., Landis, W.J.: Molecular basis for elastic energy storage in mineralized tendon. Biomacromolecules 2, 750–756 (2001)
Wolinsky, H., Seymour, G.: A lamellar unit of aortic medial structure and function in mammals. Circ. Res. 20, 99–111 (1967)
Clark, J.M., Glagov, S.: Transmural organization of the arterial media—the lamellar unit revisited. Arteriosclerosis 5, 19–34 (1985)
Wolinsky, H., Seymour, G.: Comparison of abdominal and thoracic aortic medial structure in mammals. Circ. Res. 25, 677–686 (1969)
Hallock, P., Benson, I.C.: Studies on the elastic properties of human isolated aorta. J. Clin. Invest. 16, 595–602 (1937)
Åstrand, H., Stålhand, J., Karlsson, M., Sonesson, B., Länne, T.: In vivo estimation of the contribution of elastin and collagen to the mechanical properties in the human abdominal aorta: effects of age and sex. J. Appl. Phys. 110:176–187 (2011)
O’Connell, M.K., Murthy, S., Phan, S., Xu, C., Buchanan, J., Spilker, R., Dalman, R.L., Zarins, C.K., Denk, W., Taylor, C.A.: The three-dimensional micro- and nanostructure of the aortic medial lamellar unit measured using 3D confocal and electron microscopy imaging. Matrix Biol. 27, 171–181 (2008)
Behmoaras, J., Osborne-Pellegrin, M., Gauguier, D., Jacob, M.P.: Characteristics of the aortic elastic network and related phenotypes in seven inbred rat strains. Am. J. Physiol. Heart. Circ. Physiol. 288, 769–777 (2005)
Merrilees, M., Tiang, K.M., Scott, L.: Changes in collagen fibril diameters across artery walls including a correlation with glycosaminoglycan content. Connect. Tissue Res. 16, 237–257 (1987)
Rachev, A., Stergiopulos, N., Meister, J.J.: Theoretical study of dynamics of arterial wall remodeling in response to changes in blood pressure. J. Biomech. 29, 635–642 (1996)
Zhang, W., Herrera, C., Atluri, S.N., Kassab, G.S.: The effect of longitudinal pre-stretch and radial constraint on the stress distribution in the vessel wall: a new hypothesis. Mech. Chem. Biosyst. 2, 41–52 (2005)
Kassab, G.S.: Biomechanics of the cardiovascular system: the aorta as an illustratory example. J. R. Soc. Interface 3, 719–740 (2006)
Fung, Y.C.: Biorheology of soft tissues. Biorheology 10, 199–212 (1973)
Yin, L., Elliott, D.M.: A biphasic and transversely isotropic mechanical model for tendon: application to mouse tail fascicles in uniaxial tendons. J. Biomech. 37, 907–916 (2004)
Comninou, M., Yannas, I.V.: Dependance of stress–strain nonlinearity of connective tissues on the geometry of collagen fibers. J. Biomech. 9, 427–433 (1976)
Lanir, Y.: A structural theory for the homogeneous biaxial stress–strain relationships in flat collagenous tissues. J. Biomech. 12, 423–436 (1979)
Freed, A.D., Doehring, T.C.: Elastic model for crimped collagen fibrils. J. Biomech. Eng. 127, 587–593 (2005)
Holzapfel, G.A., Gasser, T.C., Ogden, R.W.: A new constitutive framework for arterial wall mechanics and a comparative study of material models. J. Elast. 61, 1–48 (2000)
Holzapfel, G.A., Gasser, T.C., Stadler, M.: A structural model for the viscoelastic behavior of arterial walls: continuum formulation and finite element analysis. Eur. J. Mech. A Solids 21, 441–463 (2002)
Ciarletta, P., Micera, S., Accoto, D., Dario, P.: A novel microstructural approach in tendon viscoelastic modelling at the fibrillar level. J. Biomech. 39, 2034–2042 (2006)
Tang, H., Buehler, M.J., Moran, B.: A constitutive model of soft tissue: from nanoscale collagen to tissue continuum. Ann. Biomed. Eng. 37, 1117–1130 (2009)
Maceri, F., Marino, M., Vairo, G.: From cross-linked collagen molecules to arterial tissue: a nano-micro-macroscale elastic model. Acta Mech. Solida Sin. 23(S1), 98–108 (2010)
Marino, M., Vairo, G.: Stress and strain localization in stretched collagenous tissues via a multiscale modeling approach. Comput. Methods Biomech. Biomed. Engin. (2012). doi:10.1080/10255842.2012.658043
Maceri, F., Marino, M., Vairo, G.: An insight on multiscale tendon modeling in muscle-tendon integrated behavior. Biomech. Model. Mechanobiol. 11, 505–517 (2011)
Bozec, L., Horton, M.: Topography and mechanical properties of single molecules of type I collagen using atomic force microscopy. Biophys. J. 88, 4223–4231 (2005)
Holmes, D.F., Graham, H.K., Trotter, J.A., Kadler, K.E.: STEM/TEM studies of collagen fibril assembly. Micron 32, 273–285 (2001)
Buehler, M.J.: Nanomechanics of collagen fibrils under varying cross-link densities: atomistic and continuum studies. J Mech. Behav. Biomed. Mat. 1, 59–67 (2008)
Bailey, A.J.: Molecular mechanisms of ageing in connective tissues. Mech. Ageing Dev. 122, 735–755 (2001)
Couppé, C., Hansen, P., Kongsgaard, M., Kovanen, V., Suetta, C., Aagaard, P., Kjær, M., Magnusson, S.P.: Mechanical properties and collagen cross-linking of the patellar tendon in old and young men. J. Appl. Physiol. 107:880–886 (2009)
Marino, M., Vairo, G.: Equivalent stiffness and compliance of curvilinear elastic fibers. In: Maceri, F., Frémond, M. (eds.) Mechanics, Models and Methods in Civil Engineering. Lecture Notes in Applied & Computational Mechanics, vol. 61, pp. 309–332. Springer, Berlin (2011)
Kollar, L.P., Springer, G.S.: Mechanics of Composite Structures. Cambridge University Press, Cambridge (2003)
Screen, H.R.C., Lee, D.A., Bader, D.L., Shelton, J.C.: An investigation into the effects of the hierarchical structure of tendon fascicles on micromechanical properties. Proc. Inst. Mech. Eng. 218, 109–119 (2004)
Lavagnino, M., Arnoczky, S.P., Caballero, O., Kepich, E., Haut R., C.: A finite element model predicts the mechanotrasduction of tendon cells to cyclic tensile loading. Biomech. Model. Mechanobiol. 7, 405–416 (2008)
Auricchio, F., Sacco, E., Vairo, G.: A mixed FSDT finite element for monoclinic laminated plates. Comput. Struct. 84, 624–639 (2006)
Zulliger, M.A., Rachev, A., Stergiopulos, N.: A constitutive formulation of arterial mechanics including vascular smooth muscle tone. Am. J. Physiol. Heart Circ. Physiol. 287, 1335–1343 (2004)
Åstrand, H., Rydén-Ahlgren, Å., Sandgren, T., Länne, T.: Age-related increase in wall stress of the human abdominal aorta: an in vivo study. J. Vasc. Surg. 42:926–931 (2005)
Cattell, M.A., Anderson, J.C., Hasleton, P.S.: Age-related changes in amounts and concentrations of collagen and elastin in normotensive human thoracic aorta. Clin. Chim. Acta 245, 73–84 (1996)
Marklund, E., Varna, J.: Modeling the effect of helical fiber structure on wood fiber composite elastic properties. Appl. Compos. Mater. 16, 245–262 (2009)
Acknowledgments
Authors would like to thank Professor Franco Maceri for valuable suggestions and fruitful discussions on this paper.
This work was developed within the framework of Lagrange Laboratory, a European research group comprising CNRS, CNR, the Universities of Rome “Tor Vergata”, Calabria, Cassino, Pavia, and Salerno, Ecole Polytechnique, University of Montpellier II, ENPC, LCPC, and ENTPE.
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Appendix
Appendix
The incremental elastic equilibrium solution for the multi-layered aortic cylinder, comprising \(N\) identical media lamellar units (MLUs) and loaded with a uniform internal pressure increment \(\dot{p}\), is herein briefly reported. Reference is made to the linearly elastic solution proposed in [67], considering the problem as an axisymmetric generalized plane strain problem, characterized by a given non-vanishing constant direct strain increment \(\dot{\varepsilon}_o\) along the cylinder axis \(z\). Accordingly, for the \(k\)th MLU, the incremental components of the displacement field in a cylindrical system of coordinates result in
The non-trivial increments of strain components are
and the components of stress increments are
where
with the index \(q=z,\varphi,\rho,\gamma\) corresponding to the \(g\)-index values \(g=1,2,3,6\), respectively, and with
\(\bar{C}_{ij}^k\) denoting the \((i,j)\) component of the stiffness matrix \({\mathbb{\bar C}}^k\) for the \(k\)th MLU.
It is worth pointing out that during the deformation path both strain and stress components, and thereby also the strain-dependent MTU material properties, are \(z\)- and \(\varphi\)-independent.
Assuming the MLUs as perfectly bonded layers, the \(3N\) unknown constants \(A_1^k,\,A_2^k,\,B^k\) (with \(k=1...N\)) are solved by imposing the following \(3(N-1)\) continuity conditions at the MLU’s interfaces:
and the three equilibrium incremental relationships:
the latter prescribing the average torque related to the tangential stress increment \(\dot{\tau}_{z\varphi}\) to be zero.
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Marino , M., Vairo, G. (2013). Multiscale Elastic Models of Collagen Bio-structures: From Cross-Linked Molecules to Soft Tissues. In: Gefen, A. (eds) Multiscale Computer Modeling in Biomechanics and Biomedical Engineering. Studies in Mechanobiology, Tissue Engineering and Biomaterials, vol 14. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8415_2012_154
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