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Research Papers

Functionally Distinct Tendons From Elastin Haploinsufficient Mice Exhibit Mild Stiffening and Tendon-Specific Structural Alteration

[+] Author and Article Information
Jeremy D. Eekhoff

Department of Biomedical Engineering,
Washington University in St. Louis
One Brookings Drive,
St. Louis, MO 63130

Fei Fang

Department of Mechanical Engineering
and Materials Science,
Washington University in St. Louis,
One Brookings Drive,
St. Louis, MO 63130

Lindsey G. Kahan, Gabriela Espinosa, Austin J. Cocciolone

Department of Biomedical Engineering,
Washington University in St. Louis,
One Brookings Drive,
St. Louis, MO 63130

Jessica E. Wagenseil

Department of Mechanical Engineering and
Materials Science,
Washington University in St. Louis,
One Brookings Drive,
St. Louis, MO 63130

Robert P. Mecham

Department of Cell Biology and Physiology,
Washington University in St. Louis,
660 South Euclid Avenue,
St. Louis, MO 63110

Spencer P. Lake

Department of Mechanical Engineering and
Materials Science,
Washington University in St. Louis,
One Brookings Drive,
St. Louis, MO 63130;
Department of Biomedical Engineering,
Washington University in St. Louis,
One Brookings Drive,
St. Louis, MO 63130;
Department of Orthopaedic Surgery,
Washington University in St. Louis,
One Brookings Drive,
St. Louis, MO 63130
e-mail: lake.s@wustl.edu

1Corresponding author.

Manuscript received August 14, 2017; final manuscript received September 11, 2017; published online September 27, 2017. Assoc. Editor: Kyle Allen.

J Biomech Eng 139(11), 111003 (Sep 27, 2017) (9 pages) Paper No: BIO-17-1362; doi: 10.1115/1.4037932 History: Received August 14, 2017; Revised September 11, 2017

Elastic fibers are present in low quantities in tendon, where they are located both within fascicles near tenocytes and more broadly in the interfascicular matrix (IFM). While elastic fibers have long been known to be significant in the mechanics of elastin-rich tissue (i.e., vasculature, skin, lungs), recent studies have suggested a mechanical role for elastic fibers in tendons that is dependent on specific tendon function. However, the exact contribution of elastin to properties of different types of tendons (e.g., positional, energy-storing) remains unknown. Therefore, this study purposed to evaluate the role of elastin in the mechanical properties and collagen alignment of functionally distinct supraspinatus tendons (SSTs) and Achilles tendons (ATs) from elastin haploinsufficient (HET) and wild type (WT) mice. Despite the significant decrease in elastin in HET tendons, a slight increase in linear stiffness of both tendons was the only significant mechanical effect of elastin haploinsufficiency. Additionally, there were significant changes in collagen nanostructure and subtle alteration to collagen alignment in the AT but not the SST. Hence, elastin may play only a minor role in tendon mechanical properties. Alternatively, larger changes to tendon mechanics may have been mitigated by developmental compensation of HET tendons and/or the role of elastic fibers may be less prominent in smaller mouse tendons compared to the larger bovine and human tendons evaluated in previous studies. Further research will be necessary to fully elucidate the influence of various elastic fiber components on structure–function relationships in functionally distinct tendons.

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References

Kannus, P. , 2000, “ Structure of the Tendon Connective Tissue,” Scand. J. Med. Sci. Sports, 10(6), pp. 312–320. [CrossRef] [PubMed]
Screen, H. R. C. , Berk, D. E. , Kadler, K. E. , Ramirez, F. , and Young, M. F. , 2015, “ Tendon Functional Extracellular Matrix,” J. Orthop. Res., 33(6), pp. 793–799. [CrossRef] [PubMed]
Thorpe, C. T. , Klemt, C. , Riley, G. P. , Birch, H. L. , Clegg, P. D. , and Screen, H. R. C. , 2013, “ Helical Sub-Structures in Energy-Storing Tendons Provide a Possible Mechanism for Efficient Energy Storage and Return,” Acta Biomater., 9(8), pp. 7948–7956. [CrossRef] [PubMed]
Fang, F. , and Lake, S. P. , 2015, “ Multiscale Strain Analysis of Tendon Subjected to Shear and Compression Demonstrates Strain Attenuation, Fiber Sliding, and Reorganization,” J. Orthop. Res., 33(11), pp. 1704–1712. [CrossRef] [PubMed]
Fang, F. , and Lake, S. P. , 2017, “ Experimental Evaluation of Multiscale Tendon Mechanics,” J. Orthop. Res., 35(7), pp. 1353–1365. [CrossRef] [PubMed]
Hansen, K. A. , Weiss, J. A. , and Barton, J. K. , 2002, “ Recruitment of Tendon Crimp With Applied Tensile Strain,” ASME J. Biomech. Eng., 124(1), pp. 72–77. [CrossRef]
Miller, K. S. , Connizzo, B. K. , Feeney, E. , and Soslowsky, L. J. , 2012, “ Characterizing Local Collagen Fiber Re-Alignment and Crimp Behavior Throughout Mechanical Testing in a Mature Mouse Supraspinatus Tendon Model,” J. Biomech., 45(12), pp. 2061–2065. [CrossRef] [PubMed]
Lake, S. P. , Miller, K. S. , Elliott, D. M. , and Soslowsky, L. J. , 2009, “ Effect of Fiber Distribution and Realignment on the Nonlinear and Inhomogeneous Mechanical Properties of Human Supraspinatus Tendon Under Longitudinal Tensile Loading,” J. Orthop. Res., 27(12), pp. 1596–1602. [CrossRef] [PubMed]
Thorpe, C. T. , Birch, H. L. , Clegg, P. D. , and Screen, H. R. C. , 2013, “ The Role of the Non-Collagenous Matrix in Tendon Function,” Int. J. Exp. Pathol., 94(4), pp. 248–259. [CrossRef] [PubMed]
Baldwin, A. K. , Simpson, A. , Steer, R. , Cain, S. A. , and Kielty, C. M. , 2013, “ Elastic Fibres in Health and Disease,” Expert Rev. Mol. Med., 15(e8), pp. 1–30.
Montes, G. , 1996, “ Structural Biology of the Fibres of the Collagenous and Elastic Systems,” Cell Biol. Int., 20(1), pp. 15–27. [CrossRef] [PubMed]
Sherratt, M. J. , 2009, “ Tissue Elasticity and the Ageing Elastic Fibre,” Age (Omaha), 31(4), pp. 305–325. [CrossRef]
Kostrominova, T. Y. , and Brooks, S. V. , 2013, “ Age-Related Changes in Structure and Extracellular Matrix Protein Expression Levels in Rat Tendons,” Age (Omaha), 35(6), pp. 2203–2214. [CrossRef]
Thorpe, C. T. , Riley, G. P. , Birch, H. L. , Clegg, P. D. , and Screen, H. R. C. , 2017, “ Fascicles and the Interfascicular Matrix Show Adaptation for Fatigue Resistance in Energy Storing Tendons,” Acta Biomater., 42, pp. 308–315. [CrossRef]
Sugitani, H. , Hirano, E. , Knutsen, R. H. , Shifren, A. , Wagenseil, J. E. , Ciliberto, C. , Kozel, B. A. , Urban, Z. , Davis, E. C. , Broekelmann, T. J. , and Mecham, R. P. , 2012, “ Alternative Splicing and Tissue-Specific Elastin Misassembly Act as Biological Modifiers of Human Elastin Gene Frameshift Mutations Associated With Dominant Cutis Laxa,” J. Biol. Chem., 287(26), pp. 22055–22067. [CrossRef] [PubMed]
Zeyer, K. A. , and Reinhardt, D. P. , 2015, “ Engineered Mutations in Fibrillin-1 Leading to Marfan Syndrome Act at the Protein, Cellular and Organismal Levels,” Mutat. Res. Rev. Mutat. Res., 765, pp. 7–18. [CrossRef] [PubMed]
Wu, Y. T. , Wu, P. T. , and Jou, I. M. , 2016, “ Peritendinous Elastase Treatment Induces Tendon Degeneration in Rats: A Potential Model of Tendinopathy In Vivo,” J. Orthop. Res., 34(3), pp. 471–477. [CrossRef] [PubMed]
Wu, Y.-T. , Su, W.-R. , Wu, P.-T. , Shen, P.-C. , and Jou, I.-M. , 2017, “ Degradation of Elastic Fiber and Elevated Elastase Expression in Long Head of Biceps Tendinopathy,” J. Orthop. Res., 35(9), pp. 1919–1926. [CrossRef] [PubMed]
Thakkar, D. , Grant, T. M. , Hakimi, O. , and Carr, A. J. , 2014, “ Distribution and Expression of Type VI Collagen and Elastic Fibers in Human Rotator Cuff Tendon Tears,” Connect. Tissue Res., 55(5–6), pp. 397–402. [CrossRef] [PubMed]
Gosline, J. , Lillie, M. , Carrington, E. , Guerette, P. , Ortlepp, C. , and Savage, K. , 2002, “ Elastic Proteins: Biological Roles and Mechanical Properties,” Philos. Trans. R. Soc. B Biol. Sci., 357(1418), pp. 121–132. [CrossRef]
Baldock, C. , Oberhauser, A. F. , Ma, L. , Lammie, D. , Siegler, V. , Mithieux, S. M. , Tu, Y. , Chow, J. Y. H. , Suleman, F. , Malfois, M. , Rogers, S. , Guo, L. , Irving, T. C. , Wess, T. J. , and Weiss, A. S. , 2011, “ Shape of Tropoelastin, the Highly Extensible Protein That Controls Human Tissue Elasticity,” Proc. Natl. Acad. Sci. U. S. A., 108(11), pp. 4322–4327. [CrossRef] [PubMed]
Grant, T. M. , Thompson, M. S. , Urban, J. , and Yu, J. , 2013, “ Elastic Fibres Are Broadly Distributed in Tendon and Highly Localized Around Tenocytes,” J. Anat., 222(6), pp. 573–579. [CrossRef] [PubMed]
Pang, X. , Wu, J.-P. , Allison, G. T. , Xu, J. , Rubenson, J. , Zheng, M.-H. , Lloyd, D. G. , Gardiner, B. , Wang, A. , and Kirk, T. B. , 2017, “ Three Dimensional Microstructural Network of Elastin, Collagen, and Cells in Achilles Tendons,” J. Orthop. Res., 35(6), pp. 1203–1214. [CrossRef] [PubMed]
Grant, T. M. , Yapp, C. , Chen, Q. , Czernuszka, J. T. , and Thompson, M. S. , 2015, “ The Mechanical, Structural, and Compositional Changes of Tendon Exposed to Elastase,” Ann. Biomed. Eng., 43(10), pp. 2477–2486. [CrossRef] [PubMed]
Fang, F. , and Lake, S. P. , 2016, “ Multiscale Mechanical Integrity of Human Supraspinatus Tendon in Shear After Elastin Depletion,” J. Mech. Behav. Biomed. Mater., 63, pp. 443–455. [CrossRef] [PubMed]
Henninger, H. B. , Valdez, W. R. , Scott, S. A. , and Weiss, J. A. , 2015, “ Elastin Governs the Mechanical Response of Medial Collateral Ligament Under Shear and Transverse Tensile Loading,” Acta Biomater., 25, pp. 304–312. [CrossRef] [PubMed]
Henninger, H. B. , Underwood, C. J. , Romney, S. J. , Davis, G. L. , and Weiss, J. A. , 2013, “ Effect of Elastin Digestion on the Quasi-Static Tensile Response of Medial Collateral Ligament,” J. Orthop. Res., 31(8), pp. 1226–1233. [CrossRef] [PubMed]
Li, D. Y. , Brooke, B. , Davis, E. C. , Mecham, R. P. , Sorensen, L. K. , Boak, B. B. , Eichwald, E. , and Keating, M. T. , 1998, “ Elastin is an Essential Determinant of Arterial Morphogenesis,” Nature, 393(6682), pp. 276–280. [CrossRef] [PubMed]
Li, D. Y. , Faury, G. , Taylor, D. G. , Davis, E. C. , Boyle, W. A. , Mecham, R. P. , Stenzel, P. , Boak, B. , and Keating, M. T. , 1998, “ Novel Arterial Pathology in Mice and Humans Hemizygous for Elastin,” J. Clin. Invest., 102(10), pp. 1783–1787. [CrossRef] [PubMed]
Wagenseil, J. E. , Nerurkar, N. L. , Knutsen, R. H. , Okamoto, R. J. , Li, D. Y. , Mecham, R. P. E. J. , Knut-, R. H. , and Effects, R. P. M. , 2005, “ Effects of Elastin Haploinsufficiency on the Mechanical Behavior of Mouse Arteries,” Am. J. Physiol. Hear. Circ. Physiol, 289(3), pp. H1209–H1217. [CrossRef]
Carta, L. , Wagenseil, J. E. , Knutsen, R. H. , Mariko, B. , Faury, G. , Davis, E. C. , Starcher, B. , Mecham, R. P. , and Ramirez, F. , 2009, “ Discrete Contributions of Elastic Fiber Components to Arterial Development and Mechanical Compliance,” Arterioscler. Thromb. Vasc. Biol., 29(12), pp. 2083–2089. [CrossRef] [PubMed]
Thorpe, C. T. , Karunaseelan, K. J. , Ng Chieng Hin, J. , Riley, G. P. , Birch, H. L. , Clegg, P. D. , and Screen, H. R. C. , 2016, “ Distribution of Proteins Within Different Compartments of Tendon Varies According to Tendon Type,” J. Anat., 229(3), pp. 450–458. [CrossRef] [PubMed]
Thorpe, C. T. , Godinho, M. S. C. , Riley, G. P. , Birch, H. L. , Clegg, P. D. , and Screen, H. R. C. , 2015, “ The Interfascicular Matrix Enables Fascicle Sliding and Recovery in Tendon, and Behaves More Elastically in Energy Storing Tendons,” J. Mech. Behav. Biomed. Mater., 52, pp. 85–94. [CrossRef] [PubMed]
Alexander, R. M. , 1991, “ Energy-Saving Mechanisms in Walking and Running,” J. Exp. Biol., 160, pp. 55–69. [PubMed]
Cheng, J. K. , Stoilov, I. , Mecham, R. P. , and Wagenseil, J. E. , 2013, “ A Fiber-Based Constitutive Model Predicts Changes in Amount and Organization of Matrix Proteins With Development and Disease in the Mouse Aorta,” Biomech. Model. Mechanobiol., 12(3), pp. 497–510. [CrossRef] [PubMed]
Jamall, I. S. , Finelli, V. N. , and Que Hee, S. S. , 1981, “ A Simple Method to Determine Nanogram Levels of 4-Hydroxyproline in Biological Tissues,” Anal. Biochem., 112(1), pp. 70–75. [CrossRef] [PubMed]
Neuman, R. E. , and Logan, M. A. , 1950, “ The Determination of Hydroxyproline,” J. Biol. Chem., 184(1), pp. 299–306. [PubMed]
Starcher, B. , 2001, “ A Ninhydrin-Based Assay to Quantitate the Total Protein Content of Tissue Samples,” Anal. Biochem., 292(1), pp. 125–129. [CrossRef] [PubMed]
Ricard, C. , Vial, J.-C. , Douady, J. , and van der Sanden, B. , 2015, “ In Vivo Imaging of Elastic Fibers Using Sulforhodamine B,” J. Biomed. Opt., 12(6), p. 064017. [CrossRef]
Starborg, T. , Kalson, N. S. , Lu, Y. , Mironov, A. , Cootes, T. F. , Holmes, D. F. , and Kadler, K. E. , 2013, “ Using Transmission Electron Microscopy and 3View to Determine Collagen Fibril Size and Three-Dimensional Organization,” Nat. Protoc., 8(7), pp. 1433–1448. [CrossRef] [PubMed]
York, T. , and Gruev, V. , 2012, “ Characterization of a Visible Spectrum Division-of-Focal-Plane Polarimeter,” Appl. Opt., 51(22), pp. 5392–5400. [CrossRef] [PubMed]
York, T. , Kahan, L. , Lake, S. P. , and Gruev, V. , 2014, “ Real-Time High-Resolution Measurement of Collagen Alignment in Dynamically Loaded Soft Tissue,” J. Biomed. Opt., 19(6), p. 66011. [CrossRef]
York, T. , Powell, S. B. , Gao, S. , Kahan, L. , Charanya, T. , Saha, D. , Roberts, N. W. , Cronin, T. W. , Marshall, J. , Achilefu, S. , Lake, S. P. , Raman, B. , and Gruev, V. , 2014, “ Bioinspired Polarization Imaging Sensors: From Circuits and Optics to Signal Processing Algorithms and Biomedical Applications,” Proc. IEEE. Inst. Electr. Electron. Eng., 102(10), pp. 1450–1469. [CrossRef] [PubMed]
Skelley, N. W. , Castile, R. M. , York, T. E. , Gruev, V. , Lake, S. P. , and Brophy, R. H. , 2015, “ Differences in the Microstructural Properties of the Anteromedial and Posterolateral Bundles of the Anterior Cruciate Ligament,” Am. J. Sports Med., 43(4), pp. 928–936. [CrossRef] [PubMed]
Castile, R. M. , Skelley, N. W. , Babaei, B. , Brophy, R. H. , and Lake, S. P. , 2016, “ Microstructural Properties and Mechanics Vary Between Bundles of the Human Anterior Cruciate Ligament During Stress-Relaxation,” J. Biomech., 49(1), pp. 87–93. [CrossRef] [PubMed]
Armstrong, R. A. , 2017, “ Statistical Review: Recommendations for Analysis of Repeated-Measures Designs: Testing and Correcting for Sphericity and Use of Manova and Mixed Model Analysis,” Ophthalmic Physiol. Opt., 37(5), pp. 585–593. [CrossRef] [PubMed]
Lake, S. P. , and Barocas, V. H. , 2011, “ Mechanical and Structural Contribution of Non-Fibrillar Matrix in Uniaxial Tension: A Collagen-Agarose Co-Gel Model,” Ann. Biomed. Eng., 39(7), pp. 1891–1903. [CrossRef] [PubMed]
Millesi, H. , Reihsner, R. , Hamilton, G. , Mallinger, R. , and Menzel, E. J. , 1995, “ Biomechanical Properties of Normal Tendons, Normal Palmar Aponeuroses, and Tissues From Patients With Dupuytren's Disease Subjected to Elastase and Chondroitinase Treatment,” Clin. Biomech., 10(1), pp. 29–35. [CrossRef]
Fang, F. , and Lake, S. P. , 2017, “ Multiscale Mechanical Evaluation of Human Supraspinatus Tendon Under Shear Loading After Glycosaminoglycan Reduction,” ASME J. Biomech. Eng., 139(7), p. 071013.
Fessel, G. , and Snedeker, J. G. , 2011, “ Equivalent Stiffness After Glycosaminoglycan Depletion in Tendon—An Ultra-Structural Finite Element Model and Corresponding Experiments,” J. Theor. Biol., 268(1), pp. 77–83. [CrossRef] [PubMed]
Lujan, T. J. , Underwood, C. J. , Henninger, H. B. , Thompson, B. M. , and Weiss, J. A. , 2007, “ Effect of Dermatan Sulfate Glycosaminoglycans on the Quasi-Static Material Properties of the Human Medial Collateral Ligament,” J. Orthop. Res., 25(7), pp. 894–903. [CrossRef] [PubMed]
Faury, G. , Pezet, M. , Knutsen, R. H. , Boyle, W. A. , Heximer, S. P. , McLean, S. E. , Minkes, R. K. , Blumer, K. J. , Kovacs, A. , Kelly, D. P. , Li, D. Y. , Starcher, B. , and Mecham, R. P. , 2003, “ Developmental Adaptation of the Mouse Cardiovascular System to Elastin Haploinsufficiency,” J. Clin. Invest., 112(9), pp. 1419–1428. [CrossRef] [PubMed]
Shifren, A. , Durmowicz, A. G. , Knutsen, R. H. , Hirano, E. , and Mecham, R. P. , 2006, “ Elastin Protein Levels Are a Vital Modifier Affecting Normal Lung Development and Susceptibility to Emphysema,” AJP Lung Cell. Mol. Physiol., 292(3), pp. L778–L787. [CrossRef]
Hayashi, M. , Zhao, C. , Thoreson, A. R. , Chikenji, T. , Jay, G. D. , An, K. N. , and Amadio, P. C. , 2013, “ The Effect of Lubricin on the Gliding Resistance of Mouse Intrasynovial Tendon,” PLoS One, 8(12), p. e83836. [CrossRef] [PubMed]
Kohrs, R. T. , Zhao, C. , Sun, Y. L. , Jay, G. D. , Zhang, L. , Warman, M. L. , An, K. N. , and Amadio, P. C. , 2011, “ Tendon Fascicle Gliding in Wild Type, Heterozygous, and Lubricin Knockout Mice,” J. Orthop. Res., 29(3), pp. 384–389. [CrossRef] [PubMed]
Sun, Y. L. , Wei, Z. , Zhao, C. , Jay, G. D. , Schmid, T. M. , Amadio, P. C. , and An, K. N. , 2015, “ Lubricin in Human Achilles Tendon: The Evidence of Intratendinous Sliding Motion and Shear Force in Achilles Tendon,” J. Orthop. Res., 33(6), pp. 932–937. [CrossRef] [PubMed]
Eyre, D. R. , Paz, M. A. , and Gallop, P. M. , 1984, “ Cross-Linking in Collagen and Elastin,” Ann. Rev. Biochem, 53(1), pp. 717–748. [CrossRef]
Makris, E. A. , Responte, D. J. , Paschos, N. K. , Hu, J. C. , and Athanasiou, K. A. , 2014, “ Developing Functional Musculoskeletal Tissues Through Hypoxia and Lysyl Oxidase-Induced Collagen Cross-Linking,” Proc. Natl. Acad. Sci. U. S. A., 111(45), pp. E4832–E4841. [CrossRef] [PubMed]
Eleswarapu, S. V. , Responte, D. J. , and Athanasiou, K. A. , 2011, “ Tensile Properties, Collagen Content, and Crosslinks in Connective Tissues of the Immature Knee Joint,” PLoS One, 6(10), p. e26178. [CrossRef] [PubMed]
Thorpe, C. T. , Stark, R. J. F. , Goodship, A. E. , and Birch, H. L. , 2010, “ Mechanical Properties of the Equine Superficial Digital Flexor Tendon Relate to Specific Collagen Cross-Link Levels,” Equine Vet. J., 42(s38), pp. 538–543. [CrossRef]
Birch, H. L. , 2007, “ Tendon Matrix Composition and Turnover in Relation to Functional Requirements,” Int. J. Exp. Pathol., 88(4), pp. 241–248. [CrossRef] [PubMed]
Thorpe, C. T. , Udeze, C. P. , Birch, H. L. , Clegg, P. D. , and Screen, H. R. C. , 2012, “ Specialization of Tendon Mechanical Properties Results From Interfascicular Differences,” J. R. Soc. Interface, 9(76), pp. 3108–3117. [CrossRef] [PubMed]
Connizzo, B. K. , Freedman, B. R. , Fried, J. H. , Sun, M. , Birk, D. E. , and Soslowsky, L. J. , 2015, “ Regulatory Role of Collagen V in Establishing Mechanical Properties of Tendons and Ligaments Is Tissue Dependent,” J. Orthop. Res., 33(6), pp. 882–888. [CrossRef] [PubMed]
Connizzo, B. K. , Bhatt, P. R. , Liechty, K. W. , and Soslowsky, L. J. , 2014, “ Diabetes Alters Mechanical Properties and Collagen Fiber Re-Alignment in Multiple Mouse Tendons,” Ann. Biomed. Eng., 42(9), pp. 1880–1888. [CrossRef] [PubMed]

Figures

Grahic Jump Location
Fig. 1

Images of a representative SST and AT prior to ramp to failure taken using the QPLI system. The bone is fixed on the left, and the free end of the tendon is clamped on the right. Stain lines, outlined with dotted lines, mark the boundaries of the ROI for analysis of DoLP and AoP. Data are analyzed as groups of pixels, where the AVG DoLP and STD AoP represent the strength of alignment and uniformity of orientation, respectively.

Grahic Jump Location
Fig. 2

CSA was greater in ATs than SSTs and was unaffected by genotype (a). Elastin content was decreased in HET tendons and was similar between tendon types (b). Collagen content was decreased in ATs and was unaffected by genotype (c). Two-way ANOVA *genotype effect p < 0.05; #tendon type effect p < 0.05.

Grahic Jump Location
Fig. 3

Distribution of SRB-stained elastic fibers (bright cyan; white arrows), tenocytes (blue), and collagen (cyan) in WT and HET SSTs and ATs. Few or no fibers were visible in SSTs (a,b). Stained fibers are visible in WT and HET ATs (c,d), where they conformed to collagen orientation and were often localized near tenocytes. No differences were evident between genotypes. Scale bar = 50 μm. Refer to online version for color figure.

Grahic Jump Location
Fig. 4

Representative TEM micrographs from WT and HET SSTs and ATs (a,b,e,f). Scale bar = 500 nm. Elastin haploinsufficiency caused no change in SST collagen nanostructure (c,d), while HET ATs had decreased area fraction (g) and altered fibril diameter distribution (h). *Genotype effect p < 0.05.

Grahic Jump Location
Fig. 5

Representative TEM micrograph from a HET SST showing groups of fibrillin microfibrils with varying amounts of elastin, circled in white. Scale bar = 500 nm.

Grahic Jump Location
Fig. 6

Changes in collagen alignment during stress relaxation are represented by AVG DoLP and STD AoP. In both tendons, AVG DoLP decreased (a,c) and STD AoP increased (b,d) as time progressed. There was a trend toward decreased STD AoP in HET ATs compared to WT ATs. Note: The initial time of the test was set to 1 s to allow graphical representation on a logarithmic scale. AVG DoLP y-axes do not start at 0.

Grahic Jump Location
Fig. 7

Toe stiffness was similar across both genotypes and tendon types (a). Linear stiffness was greater in ATs and was increased in HET tendons (b). Transition displacement and transition force were greater in ATs and not affected by genotype (c,d). Two-way ANOVA *genotype effect p < 0.05; #tendon type effect p < 0.05.

Grahic Jump Location
Fig. 8

Changes in collagen alignment during ramp to failure are represented by AVG DoLP and STD AoP. In both tendons, AVG DoLP increased (a,c) and STD AoP decreased (b,d) with increasing strain. There was a greater increase in AVG DoLP from initial to transition regions and a trend toward decreased STD AoP in HET ATs compared to WT ATs. Note: AVG DoLP y-axes do not start at 0.

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