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Biophysical Reviews

, Volume 2, Issue 3, pp 121–135 | Cite as

Multi-dimensional correlative imaging of subcellular events: combining the strengths of light and electron microscopy

  • Yingying Su
  • Marko Nykanen
  • Kristina A. Jahn
  • Renee Whan
  • Laurence Cantrill
  • Lilian L. Soon
  • Kyle R. Ratinac
  • Filip Braet
Review

Abstract

To genuinely understand how complex biological structures function, we must integrate knowledge of their dynamic behavior and of their molecular machinery. The combined use of light or laser microscopy and electron microscopy has become increasingly important to our understanding of the structure and function of cells and tissues at the molecular level. Such a combination of two or more different microscopy techniques, preferably with different spatial- and temporal-resolution limits, is often referred to as ‘correlative microscopy’. Correlative imaging allows researchers to gain additional novel structure–function information, and such information provides a greater degree of confidence about the structures of interest because observations from one method can be compared to those from the other method(s). This is the strength of correlative (or ‘combined’) microscopy, especially when it is combined with combinatorial or non-combinatorial labeling approaches. In this topical review, we provide a brief historical perspective of correlative microscopy and an in-depth overview of correlative sample-preparation and imaging methods presently available, including future perspectives on the trend towards integrative microscopy and microanalysis.

Keywords

Correlative morphomics Combinatorial labeling Combined microscopy Live-cell imaging Integrated microscopy Electron tomography 

Notes

Acknowledgments

The authors acknowledge the facilities, as well as technical and administrative assistance from staff, of the AMMRF at the Australian Centre for Microscopy & Microanalysis of the University of Sydney, and are particularly grateful to Ellie Kable and Deborah Barton. We also thank the Australian Research Council (ARC) for funding some of the research reported herein through ‘Linkage Infrastructure, Equipment and Facilities’- (LE0775598, LE0883030 & LE100100010) and ‘Discovery Project’ grants (DP0881012), as well as support from the ARC/NHMRC FABLS Research Network (RN0460002).

References

  1. Agronskaia AV, Valentijn JA, van Driel LF, Schneijdenberg CT, Humbel BM, van Bergen En Henegouwen PM, Verkleij AJ, Koster AJ, Gerritsen HC (2008) Integrated fluorescence and transmission electron microscopy. J Struct Biol 164:183–189Google Scholar
  2. Albrecht RM, Goodman SL, Simmons SR (1989) Distribution and movement of membrane-associated platelet glycoproteins: use of colloidal gold with correlative video-enhanced light microscopy, low-voltage high-resolution scanning electron microscopy, and high-voltage transmission electron microscopy. Am J Anat 185:149–164CrossRefPubMedGoogle Scholar
  3. Albrecht RM, Olorundare OE, Simmons SR, Loftus JC, Mosher DF (1992) Use of correlative microscopy with colloidal gold labeling to demonstrate platelet receptor distribution and movement. Methods Enzymol 215:456–479CrossRefPubMedGoogle Scholar
  4. Biel SS, Kawaschinski K, Wittern KP, Hintze U, Wepf R (2003) From tissue to cellular ultrastructure: closing the gap between micro- and nanostructural imaging. J Microsc 212:91–99CrossRefPubMedGoogle Scholar
  5. Braet F, Ratinac K (2007) Creating next-generation microscopists: structural and molecular biology at the crossroads. J Cell Mol Med 11:759–763CrossRefPubMedGoogle Scholar
  6. Braet F, Geerts WJ (2009) Foreword to the themed issue on correlative microscopy. J Microsc 235:239–240CrossRefPubMedGoogle Scholar
  7. Braet F, Spector I, Shochet NR, Crews P, Higa T, Menu E, De Zanger R, Wisse E (2002) The new anti-actin agent dihydrohalichondramide reveals fenestrae-forming centers in hepatic endothelial cells. BMC Cell Biol 3:7CrossRefPubMedGoogle Scholar
  8. Braet F, Wisse E, Bomans P, Frederik P, Geerts W, Koster A, Soon L, Ringer S (2007) Contribution of high-resolution correlative imaging techniques in the study of the liver sieve in three-dimensions. Microsc Res Tech 70:230–242CrossRefPubMedGoogle Scholar
  9. Burton GJ, Thurley KW, Skepper JN (1991) A technique for correlative scanning and transmission electron microscopy of individual human placental villi: an example demonstrating syncytial sprouts in early gestation. Scan Microsc 5:451–458Google Scholar
  10. Capani F, Saraceno E, Boti VR, Aon-Bertolino L, Fernández JC, Gato F, Kruse MS, Giraldez L, Ellisman MH, Coirini H (2008) A tridimensional view of the organization of actin filaments in the central nervous system by use of fluorescent photooxidation. Biocell 32:1–8PubMedGoogle Scholar
  11. Chang JC, Su HL, Hsu SH (2008) The use of peptide-delivery to protect human adipose-derived adult stem cells from damage caused by the internalization of quantum dots. Biomaterials 29:925–936CrossRefPubMedGoogle Scholar
  12. Chen I, Ting AY (2005) Site-specific labeling of proteins with small molecules in live cells. Curr Opin Biotechnol 16:35–40CrossRefPubMedGoogle Scholar
  13. Cheutin T, Sauvage C, Tchélidzé P, O'Donohue MF, Kaplan H, Beorchia A, Ploton D (2007) Visualizing macromolecules with fluoronanogold: from photon microscopy to electron tomography. Methods Cell Biol 79:559–574CrossRefPubMedGoogle Scholar
  14. Cowieson NP, Kobe B, Martin JL (2008) United we stand: combining structural methods. Curr Opin Struct Biol 18:617–622CrossRefPubMedGoogle Scholar
  15. Dahan M, Lévi S, Luccardini C, Rostaing P, Riveau B, Triller A (2003) Diffusion dynamics of glycine receptors revealed by single-quantum dot tracking. Science 302:442–445CrossRefPubMedGoogle Scholar
  16. Darien BJ, Sims PA, Kruseelliott KT, Homan TS, Cashwell RJ, Cooley AJ, Albrecht RM (1995) Use of colloidal gold and neutron-activation in correlative microscopic labeling and label quantitation. Scan Microsc 9:773–780Google Scholar
  17. Deerinck TJ (2008) The application of fluorescent quantum dots to confocal, multiphoton, and electron microscopic imaging. Toxicol Pathol 36:112–116CrossRefPubMedGoogle Scholar
  18. Deerinck TJ, Martone ME, Lev-Ram V, Green DP, Tsien RY, Spector DL, Huang S, Ellisman MH (1994) Fluorescence photooxidation with eosin: a method for high resolution immunolocalization and in situ hybridization detection for light and electron microscopy. J Cell Biol 126:901–910CrossRefPubMedGoogle Scholar
  19. Deerinck TJ, Giepmans BNG, Smarr BL, Martone ME, Ellisman MH (2007) Light and electron microscopic localization of multiple proteins using quantum dots. Methods Mol Biol 374:43–53PubMedGoogle Scholar
  20. DeFelipe J, Fairén A (1993) A simple and reliable method for correlative light and electron microscopic studies. J Histochem Cytochem 41:769–772PubMedGoogle Scholar
  21. Derfus AM, Chan WCW, Bhatia SM (2004) Intracellular delivery of quantum dots for live cell labeling and organelle tracking. Adv Mater 16:961–966CrossRefGoogle Scholar
  22. Donnell C, Hyde B, Dowling EA (1988) Correlative light and scanning electron-microscopy of endometrium in postmenopausal hormone replacement candidates. Mod Pathol 1:A25–A25Google Scholar
  23. Dubertret B, Skourides P, Norris DJ, Noireaux V, Brivanlou AH, Libchaber A (2002) In vivo imaging of quantum dots encapsulated in phospholipid micelles. Science 298:1759–1762CrossRefPubMedGoogle Scholar
  24. Ellis EA (2008) Correlative transmission microscopy: cytochemical localization and immunocytochemical localization in studies of oxidative and nitrosative stress. Methods Mol Biol 477:41–48CrossRefPubMedGoogle Scholar
  25. Fomina AF, Deerinck TJ, Ellisman MH, Cahalan MD (2003) Regulation of membrane trafficking and subcellular organization of endocytic compartments revealed with FM1-43 in resting and activated human T cells. Exp Cell Res 291:150–166CrossRefPubMedGoogle Scholar
  26. Frey TG, Sun MG (2008) Correlated light and electron microscopy illuminates the role of mitochondrial inner membrane remodeling during apoptosis. Biochim Biophys Acta 1777:847–852CrossRefPubMedGoogle Scholar
  27. Fucikova A, Valenta J, Pelant I, Brezina V (2009) Novel use of silicon nanocrystals and nanodiamonds in biology. Chem Pap 63:704–708CrossRefGoogle Scholar
  28. Geissinger HD (1974) A precise stage arrangement for correlative microscopy for specimens mounted on glass slides, stubs or EM grids. J Microsc 100:113–117Google Scholar
  29. Giepmans BN (2008) Bridging fluorescence microscopy and electron microscopy. Histochem Cell Biol 130:211–217CrossRefPubMedGoogle Scholar
  30. Giepmans BN, Deerinck TJ, Smarr BL, Jones YZ, Ellisman MH (2005) Correlated light and electron microscopic imaging of multiple endogenous proteins using Quantum dots. Nat Methods 10:743–749CrossRefGoogle Scholar
  31. Goodman SL, Albrecht RM (1987) Correlative light and electron-microscopy of platelet-adhesion and fibrinogen receptor expression using colloidal-gold labeling. Scan Microsc 1:727–734Google Scholar
  32. Grabenbauer M, Geerts WJ, Fernadez-Rodriguez J, Hoenger A, Koster AJ, Nilsson T (2005) Correlative microscopy and electron tomography of GFP through photooxidation. Nat Methods 14:857–862CrossRefGoogle Scholar
  33. Hainfeld JF, Furuya FR (1992) A 1.4-nm gold cluster covalently attached to antibodies improves immunolabeling. J Histochem Cytochem 40:177–184PubMedGoogle Scholar
  34. Hekking LH, Lebbink MN, De Winter DA, Schneijdenberg CT, Brand CM, Humbel BM, Verkleij AJ, Post JA (2009) Focused ion beam-scanning electron microscope: exploring large volumes of atherosclerotic tissue. J Microsc 235:336–347CrossRefPubMedGoogle Scholar
  35. Hirabayashi Y, Yamada K (1998) A histochemical approach to correlative light and electron microscopic detection of acidic glycoconjugates by a sensitized high iron diamine method. J Histochem Cytochem 46:767–770PubMedGoogle Scholar
  36. Ho Y-P, Leong KW (2010) Quantum dot-based theranostics. Nanoscale 2:60–68CrossRefPubMedGoogle Scholar
  37. Hwang RD, Chen CC, Knecht DA (2009) ReAsH: another viable option for in vivo protein labelling in Dictyostelium. J Microsc 234:9–15CrossRefPubMedGoogle Scholar
  38. Jahn KA, Braet F (2008) Monitoring membrane rafts in colorectal cancer cells by means of correlative fluorescence electron microscopy (CFEM). Micron 39:1393–1397CrossRefPubMedGoogle Scholar
  39. Jahn K, Barton D, Braet F (2007) Correlative fluorescence- and scanning, transmission electron microscopy for biomolecular investigation. In: Díaz J, Méndez-Vilas A (eds) Modern research and educational topics in microscopy. Formatex Press, Badajoz, pp 203–211Google Scholar
  40. Jahn KA, Barton DA, Su Y, Riches J, Kable EPW, Soon LL, Braet F (2009) Correlative fluorescence and transmission electron microscopy imaging of the actin cytoskeleton of whole-mount (breast) cancer cells. J Microsc 235:282–292CrossRefPubMedGoogle Scholar
  41. Kushida T, Nagato Y, Iijima H, Kushida H (1993) Correlative light and electron microscopy of the same sections embedded in HPMA, Quetol 523 and MMA. Okajimas Folia Anat Jpn 69:277–287PubMedGoogle Scholar
  42. Larson DR, Zipfel WR, Williams RM, Clark SW, Bruchez MP, Wise FW, Webb WW (2003) Water-soluble quantum dots for multiphoton fluorescence imaging in vivo. Science 300:1434–1436CrossRefPubMedGoogle Scholar
  43. Lin MZ, Wang L (2008) Selective labeling of proteins with chemical probes in living cells. Physiology 23:131–141CrossRefPubMedGoogle Scholar
  44. Lübke J (1993) Photoconversion of diaminobenzidine with different fluorescent neuronal markers into a light and electron microscopic dense reaction product. Microsc Res Tech 24:2–14CrossRefPubMedGoogle Scholar
  45. Martin BR, Giepmans BN, Adams SR, Tsien RY (2005) Mammalian cell-based optimization of the biarsenical binding tetracycteine motif for improved fluorescence and affinity. Nat Biotechnol 23:1308–1314CrossRefPubMedGoogle Scholar
  46. Mattheakis LC, Dias JM, Choi Y-J, Gong J (2004) Optical coding of mammalian cells using semiconductor quantum dots. Anal Biochem 327:200–208CrossRefPubMedGoogle Scholar
  47. McCann CM, Bareyre FM, Lichtman JW, Sanes JR (2005) Peptide tags for labeling membrane proteins in live cells with multiple fluorophores. Biotechniques 38:945–952CrossRefPubMedGoogle Scholar
  48. McDonald K (2009) A review of high-pressure freezing preparation techniques for correlative light and electron microscopy of the same cells and tissues. J Microsc 235:273–281CrossRefPubMedGoogle Scholar
  49. McDonald LW, Hayes TL (1969) Correlation of scanning electron microscope and light microscope images of individual cells in human blood and blood clots. Exp Mol Pathol 10:186–198CrossRefPubMedGoogle Scholar
  50. Meißlitzer-Ruppitsch C, Röhrl CR, Neumuller J, Pavelka M, Ellinger A (2009) Photooxidation technology for correlated light and electron microscopy. J Microsc 235:322–335CrossRefPubMedGoogle Scholar
  51. Miller SE, Howell DN (1997) Concerted use of immunologic and ultrastructural analyses in diagnostic medicine: Immunoelectron microscopy and correlative microscopy. Immunol Invest 26:29–38CrossRefPubMedGoogle Scholar
  52. Mironov AA, Beznoussenko GV (2009) Correlative microscopy: a potent tool for the study of rare or unique cellular and tissue events. J Microsc 235:308–321CrossRefPubMedGoogle Scholar
  53. Mironov AA, Polishchuk RS, Luini A (2000) Visualizing membrane traffic in vivo by combined video fluorescence and 3D electron microscopy. Trends Cell Biol 8:349–353CrossRefGoogle Scholar
  54. Monosov EZ, Wenzel TJ, Lüers GH, Heyman JA, Subramani S (1996) Labeling of peroxisomes with green fluorescent protein in living P. pastoris cells. J Histochem Cytochem 44:581–589PubMedGoogle Scholar
  55. Morphew MHW, Bjorkman PJ, McIntosh JR (2008) Silver enhancement of nanogold particles during freeze substitution for electron microscopy. J Microsc 230:263–267CrossRefPubMedGoogle Scholar
  56. Nishiyama H, Suga M, Ogura T, Maruyama Y, Koizumi M, Mio K, Kitamura S, Sato C (2010) Atmospheric scanning electron microscope observes cells and tissues in open medium through silicon nitride film. J Struct Biol 169:438–449CrossRefPubMedGoogle Scholar
  57. Nisman R, Dellaire G, Ren Y, Li R, Bazett-Jones DP (2004) Application of quantum dots as probes for correlative fluorescence, conventional, and energy-filtered transmission electron microscopy. J Histochem Cytochem 52:13–18PubMedGoogle Scholar
  58. Nixon SJ, Webb RI, Floetenmeyer M, Schieber N, Lo HP, Parton RG (2009) A single method for cryofixation and correlative light, electron microscopy and tomography of zebrafish embryos. Traffic 10:131–136CrossRefPubMedGoogle Scholar
  59. Nykänen M (2009) Correlation of light with electron microscopy: a correlative microscopy platform. In: Goldys EM (ed) Fluorescence applications in biotechnology and life sciences. Wiley-Blackwell, Hoboken, pp 141–156Google Scholar
  60. Oehring H, Halbhuber KJ (1991) Employment of merocyanine 540 fluorescence to form diaminobenzidine (DAB) oxidation product: a photoconversion method for the visualization of erythrocyte membrane fluidity for light and electron microscopy. Acta Histochem 90:127–134PubMedGoogle Scholar
  61. Pagano RE, Sepanski MA, Martin OC (1989) Molecular trapping of a fluorescent ceramide analogue at the Golgi apparatus of fixed cells: interaction with endogenous lipids provides a trans-Golgi marker for both light and electron microscopy. J Cell Biol 109:2067–2079CrossRefPubMedGoogle Scholar
  62. Park H, Hanson GT, Duff SR, Selvin PR (2004) Nanometre localization of single ReAsH molecules. J Microsc 216:199–205CrossRefPubMedGoogle Scholar
  63. Peachey LD, Ishikawa H, Murakami T (1996) Correlated confocal and intermediate voltage electron microscopy imaging of the same cells using sequential fluorescence labeling, fixation, and critical point dehydration. Scan Microsc 10:237–247Google Scholar
  64. Peng XG (2003) Mechanisms for the shape-control and shape-evolution of colloidal semiconductor nanocrystals. Adv Mater 15:459–463CrossRefGoogle Scholar
  65. Perinetti G, Müller T, Spaar A, Polishchuk R, Luini A, Egner A (2009) Correlation of 4Pi and electron microscopy to study transport through single Golgi stacks in living cells with super resolution. Traffic 10:379–391CrossRefPubMedGoogle Scholar
  66. Plitzko JM, Rigort A, Leis A (2009) Correlative cryo-light microscopy and cryo-electron tomography: from cellular territories to molecular landscapes. Curr Opin Biotechnol 20:83–89CrossRefPubMedGoogle Scholar
  67. Powell RD, Halsey CM, Hainfeld JF (1998) Combined fluorescent and gold immunoprobes: reagents and methods for correlative light and electron microscopy. Microsc Res Tech 42:2–12CrossRefPubMedGoogle Scholar
  68. Rash JE, Yasumura T, Dudek FE (1998) Ultrastructure, histological distribution, and freeze-fracture immunocytochemistry of gap junctions in rat brain and spinal cord. Cell Biol Int 22:731–749CrossRefPubMedGoogle Scholar
  69. Razi M, Tooze SA (2009) Correlative light and electron microscopy. Methods Enzymol 452:261–275CrossRefPubMedGoogle Scholar
  70. Reynolds AM, Sculimbrene BR, Imperiali B (2008) Lanthanide-binding tags with unnatural amino acids: sensitizing Tb3+ and Eu3+ luminescence at longer wavelengths. Bioconjug Chem 19:588–591CrossRefPubMedGoogle Scholar
  71. Rieder CL, Bowser SS (1985) Correlative immunofluorescence and electron-microscopy on the same section of epon-embedded material. J Histochem Cytochem 33:165–171PubMedGoogle Scholar
  72. Robinson JM, Vandré DD (1997) Efficient immunocytochemical labeling of leukocyte microtubules with FluoroNanogold: an important tool for correlative microscopy. J Histochem Cytochem 45:631–642PubMedGoogle Scholar
  73. Säälik P, Padari K, Niinep A, Lorents A, Hansen M, Jokitalo E, Langel Ü, Pooga M (2009) Protein delivery with transportans is mediated by caveolae rather than flotillin-dependent pathways. Bioconjug Chem 20:877–887CrossRefPubMedGoogle Scholar
  74. Schmued LC, Snavely LF (1993) Photoconversion and electron microscopic localization of the fluorescent axon tracer fluoro-ruby (rhodamine-dextran-amine). J Histochem Cytochem 41:777–782PubMedGoogle Scholar
  75. Shaner NC, Steinbach PA, Tsien RY (2005) A guide to choosing fluorescent proteins. Nat Methods 2:905–909CrossRefGoogle Scholar
  76. Simmons SR, Pawley JB, Albrecht RM (1990) Optimizing parameters for correlative immunogold localization by video-enhanced light microscopy, high-voltage transmission electron microscopy, and field emission scanning electron microscopy. J Histochem Cytochem 38:1781–1785PubMedGoogle Scholar
  77. Sletten EM, Bertozzi CR (2009) Bioorthogonal chemistry: fishing for selectivity in a sea of functionality. Angew Chem Int Ed Eng 48:6974–6998CrossRefGoogle Scholar
  78. Smith A, Ruan G, Rhyner M, Nie S (2006) Engineering luminescent quantum dots for in vivo molecular and cellular imaging. Ann Biomed Eng 34:3–14CrossRefPubMedGoogle Scholar
  79. Sosinsky GE, Giepmans BN, Deerinck TJ, Gaietta GM, Ellisman MH (2007) Markers for correlated light and electron microscopy. Methods Cell Biol 79:575–591CrossRefPubMedGoogle Scholar
  80. Subramaniam S (2005) Bridging the imaging gap: visualizing subcellular architecture with electron tomography. Curr Opin Microbiol 8:316–322CrossRefPubMedGoogle Scholar
  81. Sun MG, Williams J, Munoz-Pinedo C, Perkins GA, Brown JM, Ellisman MH, Green DR, Frey TG (2007) Correlated three-dimensional light and electron microscopy reveals transformation of mitochondria during apoptosis. Nat Cell Biol 9:1057–1072CrossRefPubMedGoogle Scholar
  82. Sunbul M, Yen M, Zou Y, Yin J (2008) Enzyme catalyzed site-specific protein labeling and cell imaging with quantum dots. Chem Commun 45:5927–5929CrossRefGoogle Scholar
  83. Swanson JA, Peters PJ (2005) Subcellular imaging technologies - microscopic visual thinking. Curr Opin Microbiol 8:313–315CrossRefGoogle Scholar
  84. Takizawa T, Robinson JM (2000) Analysis of antiphotobleaching reagents for use with fluoronanogold in correlative microscopy. J Histochem Cytochem 48:433–436PubMedGoogle Scholar
  85. Verkade P (2008) Moving EM: the Rapid Transfer System as a new tool for correlative light and electron microscopy and high throughput for high-pressure freezing. J Microsc 230:317–328CrossRefPubMedGoogle Scholar
  86. Walling MA, Novak JA, Shepard JR (2009) Quantum dots for live cell and in vivo imaging. Int J Mol Sci 10:441–491CrossRefPubMedGoogle Scholar
  87. Walther C, Meyer K, Rennert R, Neundorf I (2008) Quantum dot-carrier peptide conjugates suitable for imaging and delivery applications. Bioconjug Chem 19:2346–2356CrossRefPubMedGoogle Scholar
  88. Wynford-Thomas D, Jasani B, Newman GR (1986) Immunohistochemical localization of cell surface receptors using a novel method permitting simple, rapid and reliable LM/EM correlation. Histochem J 18:387–396CrossRefPubMedGoogle Scholar
  89. Zhang Y, So MK, Rao J (2006) Protease-modulated cellular uptake of quantum dots. Nano Lett 6:1988–1992CrossRefPubMedGoogle Scholar
  90. Zipfel W, Williams R, Webb W (2003) Nonlinear magic: multiphoton microscopy in the biosciences. Nat Biotechnol 21:1369–1377CrossRefPubMedGoogle Scholar

Copyright information

© International Union for Pure and Applied Biophysics (IUPAB) and Springer 2010

Authors and Affiliations

  • Yingying Su
    • 1
  • Marko Nykanen
    • 2
  • Kristina A. Jahn
    • 1
  • Renee Whan
    • 1
  • Laurence Cantrill
    • 2
  • Lilian L. Soon
    • 1
  • Kyle R. Ratinac
    • 1
  • Filip Braet
    • 1
  1. 1.Australian Centre for Microscopy and MicroanalysisThe University of SydneySydneyAustralia
  2. 2.Kids Research Institute, Children’s Hospital WestmeadWestmeadAustralia

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