Hostname: page-component-8448b6f56d-sxzjt Total loading time: 0 Render date: 2024-04-20T00:25:58.671Z Has data issue: false hasContentIssue false
  • English
  • Français

Collagen Fibril Ultrastructure in Mice Lacking Discoidin Domain Receptor 1

Published online by Cambridge University Press:  22 June 2016

Jeffrey R. Tonniges ,
Benjamin Albert ,
Edward P. Calomeni ,
Shuvro Roy ,
Joan Lee ,
Xiaokui Mo ,
Susan E. Cole  and
Gunjan Agarwal
Jeffrey R. Tonniges
Affiliation:
Biophysics Graduate Program, The Ohio State University, Columbus, OH 43210, USA
Benjamin Albert
Affiliation:
Biomedical Engineering Department, The Ohio State University, Columbus, OH 43210, USA
Edward P. Calomeni
Affiliation:
Department of Pathology, The Ohio State University, Columbus, OH 43210, USA
Shuvro Roy
Affiliation:
David Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA
Joan Lee
Affiliation:
David Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA
Xiaokui Mo
Affiliation:
Center for Biostatistics, The Ohio State University, Columbus, OH 43210, USA
Susan E. Cole
Affiliation:
Department of Molecular Genetics, The Ohio State University, Columbus, OH 43210, USA
Gunjan Agarwal*
Affiliation:
Biomedical Engineering Department, The Ohio State University, Columbus, OH 43210, USA David Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA
*
*Corresponding author. agarwal.60@osu.edu
Get access

Abstract

The quantity and quality of collagen fibrils in the extracellular matrix (ECM) have a pivotal role in dictating biological processes. Several collagen-binding proteins (CBPs) are known to modulate collagen deposition and fibril diameter. However, limited studies exist on alterations in the fibril ultrastructure by CBPs. In this study, we elucidate how the collagen receptor, discoidin domain receptor 1 (DDR1) regulates the collagen content and ultrastructure in the adventitia of DDR1 knock-out (KO) mice. DDR1 KO mice exhibit increased collagen deposition as observed using Masson’s trichrome. Collagen ultrastructure was evaluated in situ using transmission electron microscopy, scanning electron microscopy, and atomic force microscopy. Although the mean fibril diameter was not significantly different, DDR1 KO mice had a higher percentage of fibrils with larger diameter compared with their wild-type littermates. No significant differences were observed in the length of D-periods. In addition, collagen fibrils from DDR1 KO mice exhibited a small, but statistically significant, increase in the depth of the fibril D-periods. Consistent with these observations, a reduction in the depth of D-periods was observed in collagen fibrils reconstituted with recombinant DDR1-Fc. Our results elucidate how DDR1 modulates collagen fibril ultrastructure in vivo, which may have important consequences in the functional role(s) of the underlying ECM.

Keywords

collagenaortadiscoidin domain receptor 1electron microscopyatomic force microscopy
Type
Biological Applications
Information
Microscopy and Microanalysis , Volume 22 , Issue 3 , June 2016 , pp. 599 - 611
Copyright
Copyright © Microscopy Society of America 2016

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Agarwal, G., Mihai, C. & Iscru, D.F. (2007). Interaction of discoidin domain receptor 1 with collagen type 1. J Mol Biol 367, 443–455.10.1016/j.jmb.2006.12.073Google Scholar
Ahmad, P.J., Trcka, D., Xue, S., Franco, C., Speer, M.Y., Giachelli, C.M. & Bendeck, M.P. (2009). Discoidin domain receptor-1 deficiency attenuates atherosclerotic calcification and smooth muscle cell-mediated mineralization. Am J Pathol 175, 2686–2696.10.2353/ajpath.2009.080734Google Scholar
Akhtar, S. (2012). Effect of processing methods for transmission electron microscopy on corneal collagen fibrils diameter and spacing. Microsc Res Tech 75, 1420–1424.10.1002/jemt.22083Google Scholar
Ameye, L., Aria, D., Jepsen, K., Oldberg, A., Xu, T. & Young, M.F. (2002). Abnormal collagen fibrils in tendons of biglycan/fibromodulin-deficient mice lead to gait impairment, ectopic ossification, and osteoarthritis. FASEB J 16, 673–680.Google Scholar
Baselt, D.R., Revel, J.P. & Baldeschwieler, J.D. (1993). Subfibrillar structure of type I collagen observed by atomic force microscopy. Biophys J 65, 2644–2655.10.1016/S0006-3495(93)81329-8Google Scholar
Bhatnagar, R.S., Qian, J.J. & Gough, C.A. (1997). The role in cell binding of a beta-bend within the triple helical region in collagen alpha 1 (I) chain: Structural and biological evidence for conformational tautomerism on fiber surface. J Biomol Struct Dyn 14, 547–560.10.1080/07391102.1997.10508155Google Scholar
Blissett, A.R., Garbellini, D., Calomeni, E.P., Mihai, C., Elton, T.S. & Agarwal, G. (2009). Regulation of collagen fibrillogenesis by cell-surface expression of kinase dead DDR2. J Mol Biol 385, 902–911.10.1016/j.jmb.2008.10.060Google Scholar
Bradshaw, A.D., Baicu, C.F., Rentz, T.J., Van Laer, A.O., Bonnema, D.D. & Zile, M.R. (2010). Age-dependent alterations in fibrillar collagen content and myocardial diastolic function: role of SPARC in post-synthetic procollagen processing. Am J Physiol Heart and Circ Physiol 298, H614–H622.10.1152/ajpheart.00474.2009Google Scholar
Bradshaw, A.D., Puolakkainen, P., Dasgupta, J., Davidson, J.M., Wight, T.N. & Helene Sage, E. (2003). SPARC-null mice display abnormalities in the dermis characterized by decreased collagen fibril diameter and reduced tensile strength. J Invest Dermatol 120, 949–955.10.1046/j.1523-1747.2003.12241.xGoogle Scholar
Brondijk, T.H.C., Bihan, D., Farndale, R.W. & Huizinga, E.G. (2012). Implications for collagen I chain registry from the structure of the collagen von Willebrand factor A3 domain complex. Proc Natl Acad Sci U S A 109, 5253–5258.Google Scholar
Chakravarti, S., Magnuson, T., Lass, J.H., Jepsen, K.J., LaMantia, C. & Carroll, H. (1998). Lumican regulates collagen fibril assembly: skin fragility and corneal opacity in the absence of lumican. J Cell Biol 141, 1277–1286.10.1083/jcb.141.5.1277Google Scholar
Chakravarti, S., Petroll, W.M., Hassell, J.R., Jester, J.V., Lass, J.H., Paul, J. & Birk, D.E. (2000). Corneal opacity in lumican-null mice: defects in collagen fibril structure and packing in the posterior stroma. Invest Ophthalmol Visual Sci 41, 3365–3373.Google Scholar
Chen, H., Liu, Y., Slipchenko, M. & Zhao, X. (2011). The layered structure of coronary adventitia under mechanical load. Biophys J 101, 2555–2562.10.1016/j.bpj.2011.10.043Google Scholar
Cheng, J. & Stoilov, I. (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, 497–510.Google Scholar
Danielson, K.G., Baribault, H., Holmes, D.F., Graham, H., Kadler, K.E. & Iozzo, R.V. (1997). Targeted disruption of decorin leads to abnormal collagen fibril morphology and skin fragility. J Cell Biol 136, 729–743.Google Scholar
Dingemans, K.P., Teeling, P., Lagendijk, J.H. & Becker, A.E. (2000). Extracellular matrix of the human aortic media: An ultrastructural histochemical and immunohistochemical study of the adult aortic media. Anat Rec 258, 1–14.10.1002/(SICI)1097-0185(20000101)258:1<1::AID-AR1>3.0.CO;2-73.0.CO;2-7>Google Scholar
Dupuis, L.E., Berger, M.G., Feldman, S., Doucette, L., Fowlkes, V., Chakravarti, S., Thibaudeau, S., Alcala, N.E., Bradshaw, A.D. & Kern, C.B. (2015). Lumican deficiency results in cardiomyocyte hypertrophy with altered collagen assembly. J Mol Cell Cardiol 84, 70–80.10.1016/j.yjmcc.2015.04.007Google Scholar
Durmowicz, A.G., Parks, W.C., Hyde, D.M., Mecham, R.P. & Stenmark, K.R. (1994). Persistence, re-expression, and induction of pulmonary arterial fibronectin, tropoelastin, and type I procollagen mRNA expression in neonatal hypoxic pulmonary hypertension. Am J Pathol 145, 1411–1420.Google Scholar
Erickson, B., Fang, M., Wallace, J.M., Orr, B.G., Les, C.M. & Banaszak Holl, M.M. (2013). Nanoscale structure of type I collagen fibrils: Quantitative measurement of D-spacing. Biotechnol J 8, 117–126.10.1002/biot.201200174Google Scholar
Farndale, R.W., Lisman, T., Bihan, D., Hamaia, S., Smerling, C.S., Pugh, N., Konitsiotis, A., Leitinger, B., de Groot, P.G., Jarvis, G.E. & Raynal, N. (2008). Cell-collagen interactions: the use of peptide toolkits to investigate collagen-receptor interactions. Biochem Soc Trans 36, 241–250.10.1042/BST0360241Google Scholar
Ferri, N., Carragher, N.O. & Raines, E.W. (2004). Role of discoidin domain receptors 1 and 2 in human smooth muscle cell-mediated collagen remodeling: Potential implications in atherosclerosis and lymphangioleiomyomatosis. Am J Pathol 164, 1575–1585.10.1016/S0002-9440(10)63716-9Google Scholar
Flynn, L.A., Blissett, A.R., Calomeni, E.P. & Agarwal, G. (2010). Inhibition of collagen fibrillogenesis by cells expressing soluble extracellular domains of DDR1 and DDR2. J Mol Biol 395, 533–543.Google Scholar
Fomovsky, G., Rouillard, A. & Holmes, J. (2012). Regional mechanics determine collagen fiber structure in healing myocardial infarcts. J Mol Cell Cardiol 52, 1083–1090.Google Scholar
Franco, C., Ahmad, P.J., Hou, G., Wong, E. & Bendeck, M.P. (2010). Increased cell and matrix accumulation during atherogenesis in mice with vessel wall-specific deletion of discoidin domain receptor 1. Circ Res 106, 1775–1783.10.1161/CIRCRESAHA.109.213637Google Scholar
Franco, C., Britto, K., Wong, E., Hou, G., Zhu, S.-N., Chen, M., Cybulsky, M.I. & Bendeck, M.P. (2009). Discoidin domain receptor 1 on bone marrow-derived cells promotes macrophage accumulation during atherogenesis. Circ Res 105, 1141–1148.10.1161/CIRCRESAHA.109.207357Google Scholar
Franco, C., Hou, G., Ahmad, P.J., Fu, E.Y.K., Koh, L., Vogel, W.F. & Bendeck, M.P. (2008). Discoidin domain receptor 1 (ddr1) deletion decreases atherosclerosis by accelerating matrix accumulation and reducing inflammation in low-density lipoprotein receptor-deficient mice. CircRes 102, 1202–1211.Google Scholar
Fu, H.-L., Sohail, A., Valiathan, R.R., Wasinski, B.D., Kumarasiri, M., Mahasenan, K.V., Bernardo, M.M., Tokmina-Roszyk, D., Fields, G.B., Mobashery, S. & Fridman, R. (2013). Shedding of discoidin domain receptor 1 by membrane-type matrix metalloproteinases. J Biol Chem 288, 12114–12129.Google Scholar
Ghazanfari, S. & Driessen-Mol, A. (2012). A comparative analysis of the collagen architecture in the carotid artery: Second harmonic generation versus diffusion tensor imaging. Biochem Biophys Res Commun 426, 54–58.10.1016/j.bbrc.2012.08.031Google Scholar
Giudici, C., Raynal, N., Wiedemann, H., Cabral, W.A., Marini, J.C., Timpl, R., Bächinger, H.P., Farndale, R.W., Sasaki, T. & Tenni, R. (2008). Mapping of SPARC/BM-40/osteonectin-binding sites on fibrillar collagens. J Biol Chem 283, 19551–19560.10.1074/jbc.M710001200Google Scholar
Gumez, L., Bensamoun, S.F., Doucet, J., Haddad, O., Hawse, J.R., Subramaniam, M., Spelsberg, T.C. & Pichon, C. (2010). Molecular structure of tail tendon fibers in TIEG1 knockout mice using synchrotron diffraction technology. J Appl Physiol 108, 1706–1710.10.1152/japplphysiol.00356.2010Google Scholar
Hechler, B., Nonne, C., Eckly, A., Magnenat, S., Rinckel, J.-Y., Denis, C.V., Freund, M., Cazenave, J.-P., Lanza, F. & Gachet, C. (2010). Arterial thrombosis: Relevance of a model with two levels of severity assessed by histologic, ultrastructural and functional characterization. J Thromb Haemost 8, 173–184.Google Scholar
Heegaard, A.-M., Corsi, A., Danielsen, C.C., Nielsen, K.L., Jorgensen, H.L., Riminucci, M., Young, M.F. & Bianco, P. (2007). Biglycan deficiency causes spontaneous aortic dissection and rupture in mice. Circulation 115, 2731–2738.10.1161/CIRCULATIONAHA.106.653980Google Scholar
Herr, A.B. & Farndale, R.W. (2009). Structural insights into the interactions between platelet receptors and fibrillar collagen. J Biol Chem 284, 19781–19785.10.1074/jbc.R109.013219Google Scholar
Horcas, I., Fernández, R., Gómez-Rodríguez, J.M., Colchero, J., Gómez-Herrero, J. & Baro, A.M. (2007). WSXM: A software for scanning probe microscopy and a tool for nanotechnology. Rev Sci Instrum 78, 013705.Google Scholar
Hou, G., Vogel, W. & Bendeck, M.P. (2001). The discoidin domain receptor tyrosine kinase DDR1 in arterial wound repair. J Clin Invest 107, 727–735.10.1172/JCI10720Google Scholar
Hulmes, D.J., Jesior, J.C., Miller, A., Berthet-Colominas, C. & Wolff, C. (1981). Electron microscopy shows periodic structure in collagen fibril cross sections. Proc Natl Acad Sci U S A 78, 3567–3571.10.1073/pnas.78.6.3567Google Scholar
Ishii, T. & Asuwa, N. (1996). Spiraled collagen in the major blood vessels. Mod Pathol 9, 843–848.Google Scholar
Jepsen, K.J., Wu, F., Peragallo, J.H., Paul, J., Roberts, L., Ezura, Y., Oldbergi, A., Birk, D.E. & Chakravarti, S. (2002). A syndrome of joint laxity and impaired tendon integrity in lumican- and fibromodulin-deficient mice. J Biol Chem 277, 35532–35540.Google Scholar
Kyriakides, T.R., Zhu, Y.H., Smith, L.T., Bain, S.D., Yang, Z., Lin, M.T., Danielson, K.G., Iozzo, R.V., LaMarca, M., McKinney, C.E., Ginns, E.I. & Bornstein, P. (1998). Mice that lack thrombospondin 2 display connective tissue abnormalities that are associated with disordered collagen fibrillogenesis, an increased vascular density, and a bleeding diathesis. J Cell Biol 140, 419–430.10.1083/jcb.140.2.419Google Scholar
Liu, X., Wu, H., Byrne, M., Krane, S. & Jaenisch, R. (1997). Type III collagen is crucial for collagen I fibrillogenesis and for normal cardiovascular development. Proc Natl Acad Sci USA 94, 1852–1856.Google Scholar
Manabe, I., Shindo, T. & Nagai, R. (2002). Gene expression in fibroblasts and fibrosis: involvement in cardiac hypertrophy. Circ Res 91, 1103–1113.10.1161/01.RES.0000046452.67724.B8Google Scholar
Norris, R.A., Damon, B., Mironov, V., Kasyanov, V., Ramamurthi, A., Moreno-Rodriguez, R., Trusk, T., Potts, J.D., Goodwin, R.L., Davis, J., Hoffman, S., Wen, X., Sugi, Y., Kern, C.B., Mjaatvedt, C.H., Turner, D.K., Oka, T., Conway, S.J., Molkentin, J.D., Forgacs, G. & Markwald, R.R. (2007). Periostin regulates collagen fibrillogenesis and the biomechanical properties of connective tissues. J Cell Biochem 101, 695–711.10.1002/jcb.21224Google Scholar
Orgel, J.P.R.O., Irving, T.C., Miller, A. & Wess, T.J. (2006). Microfibrillar structure of type I collagen in situ. Proc Natl Acad Sci U S A 103, 9001–9005.10.1073/pnas.0502718103Google Scholar
Orgel, J.P.R.O., San Antonio, J.D. & Antipova, O. (2011). Molecular and structural mapping of collagen fibril interactions. Connect Tissue Res 52, 2–17.10.3109/03008207.2010.511353Google Scholar
Rentz, T.J., Poobalarahi, F., Bornstein, P., Sage, E.H. & Bradshaw, A.D. (2007). SPARC regulates processing of procollagen I and collagen fibrillogenesis in dermal fibroblasts. J Biol Chem 282, 22062–22071.Google Scholar
Roig, B., Franco-Pons, N., Martorell, L., Tomàs, J., Vogel, W.F. & Vilella, E. (2010). Expression of the tyrosine kinase discoidin domain receptor 1 (DDR1) in human central nervous system myelin. Brain Res 1336, 22–29.10.1016/j.brainres.2010.03.099Google Scholar
Shirani, J., Pick, R., Roberts, W.C. & Maron, B.J. (2000). Morphology and significance of the left ventricular collagen network in young patients with hypertrophic cardiomyopathy and sudden cardiac death. J Am Coll Cardiol 35, 36–44.10.1016/S0735-1097(99)00492-1Google Scholar
Shrivastava, A., Radziejewski, C., Campbell, E., Kovac, L., McGlynn, M., Ryan, T.E., Davis, S., Goldfarb, M.P., Glass, D.J., Lemke, G. & Yancopoulos, G.D. (1997). An orphan receptor tyrosine kinase family whose members serve as nonintegrin collagen receptors. Mol Cell 1, 25–34.10.1016/S1097-2765(00)80004-0Google Scholar
Sivakumar, L. & Agarwal, G. (2010). The influence of discoidin domain receptor 2 on the persistence length of collagen type I fibers. Biomaterials 31, 4802–4808.10.1016/j.biomaterials.2010.02.070Google Scholar
Slack, B.E., Siniaia, M.S. & Blusztajn, J.K. (2006). Collagen type I selectively activates ectodomain shedding of the discoidin domain receptor 1: involvement of Src tyrosine kinase. J Cell Biochem 98, 672–684.10.1002/jcb.20812Google Scholar
Slatter, D.A. & Farndale, R.W. (2015). Structural constraints on the evolution of the collagen fibril: Convergence on a 1014-residue COL domain. Open Biol 5, 140220.Google Scholar
Sugita, S. & Matsumoto, T. (2013). Heterogeneity of deformation of aortic wall at the microscopic level: Contribution of heterogeneous distribution of collagen fibers in the wall. Biomed Mater Eng 23, 447–461.Google Scholar
Svensson, L., Aszódi, A., Reinholt, F.P., Fässler, R., Heinegård, D. & Oldberg, A. (1999). Fibromodulin-null mice have abnormal collagen fibrils, tissue organization, and altered lumican deposition in tendon. J Biol Chem 274, 9636–9647.10.1074/jbc.274.14.9636Google Scholar
Sweeney, S.M., Orgel, J.P., Fertala, A., McAuliffe, J.D., Turner, K.R., Di Lullo, G.A., Chen, S., Antipova, O., Perumal, S., Ala-Kokko, L., Forlino, A., Cabral, W.A., Barnes, A.M., Marini, J.C. & San Antonio, J.D. (2008). Candidate cell and matrix interaction domains on the collagen fibril, the predominant protein of vertebrates. J Biol Chem 283, 21187–21197.10.1074/jbc.M709319200Google Scholar
Vogel, W., Gish, G.D., Alves, F. & Pawson, T. (1997). The discoidin domain receptor tyrosine kinases are activated by collagen. Mol Cell 1, 13–23.Google Scholar
Vogel, W.F. (2002). Ligand-induced shedding of discoidin domain receptor 1. FEBS Lett 514, 175–180.Google Scholar
Vogel, W.F., Aszódi, A., Alves, F. & Pawson, T. (2001). Discoidin domain receptor 1 tyrosine kinase has an essential role in mammary gland development. Mol Cell Biol 21, 2906–2917.Google Scholar
Wallace, J.M., Orr, B.G., Marini, J.C. & Holl, M.M.B. (2011). Nanoscale morphology of type I collagen is altered in the Brtl mouse model of Osteogenesis Imperfecta. J Struct Biol 173, 146–152.Google Scholar
Williams, D.R., Shifley, E.T., Lather, J.D. & Cole, S.E. (2014). Posterior skeletal development and the segmentation clock period are sensitive to Lfng dosage during somitogenesis. Dev Biol 388, 159–169.10.1016/j.ydbio.2014.02.006Google Scholar
Xu, H., Raynal, N., Stathopoulos, S., Myllyharju, J., Farndale, R.W. & Leitinger, B. (2011). Collagen binding specificity of the discoidin domain receptors: Binding sites on collagens II and III and molecular determinants for collagen IV recognition by DDR1. Matrix Biol 30, 16–26.10.1016/j.matbio.2010.10.004Google Scholar
Yamamoto, S., Hitomi, J., Sawaguchi, S., Abe, H., Shigeno, M. & Ushiki, T. (2002). Observation of human corneal and scleral collagen fibrils by atomic force microscopy. Jpn J Ophthalmol 46, 496–501.10.1016/S0021-5155(02)00558-0Google Scholar
Yamamoto, S., Hitomi, J., Shigeno, M., Sawaguchi, S., Abe, H. & Ushiki, T. (1997). Atomic force microscopic studies of isolated collagen fibrils of the bovine cornea and sclera. Arch Histol Cytol 60, 371–378.10.1679/aohc.60.371Google Scholar
Supplementary material: Image

Tonniges Supplementary Material

Fig

Download Tonniges Supplementary Material(Image)
Image 6.2 MB