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Atomic Force Microscopy of Viruses

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Structure and Physics of Viruses

Part of the book series: Subcellular Biochemistry ((SCBI,volume 68))

Abstract

Atomic force microscopy (AFM) is a helpful tool to acquire nanometric-resolution images, and also to perform a certain physical characterization of specimens, including their stiffness and mechanical resilience. Besides of the wide range of applications, from materials science to biology, this technique works in a variety of conditions as long as the sample is supported on a solid surface, in air, ultra high vacuum or, most importantly for virus research, in liquids. The adaptability of this technique is also fostered by the variety of sizes of the specimens that it can dealt with, such as atoms, molecules, molecular complexes including viruses and cells, and the possibility to observe dynamic processes in real time. Indeed, AFM facilitates single molecule experiments enabling not only to see but also to touch the material under study (i.e., to undertake mechanical manipulations), and constitutes a fundamental source of information for material characterization. In particular, the study of the mechanical properties at the nanoscale of viruses and other biomolecular aggregates, is providing an important set of data which help to elaborate mechano-chemical structure/function models of molecular biomachines, expanding and complementing the information obtained by other structural techniques.

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Notes

  1. 1.

    Also especially recommended for further reading are references [3, 4, 7, 21, 22, 45, 49] listed above.

Abbreviations

AFM:

Atomic force microscopy

CCD:

Charge-coupled device

CM:

Contact mode

DM:

Dynamic mode

EDL:

Electrostatic double layer

EM:

Electron microscopy

HOPG:

Highly oriented pyrolytic graphite

JM:

Jumping mode

MVM:

Minute virus of mice

STM:

Scanning tunneling microscopy

UHV:

Ultra-high vacuum

References and Further Reading

  1. Ortega-Esteban A, Pérez-Berná AJ, Menéndez-Conejero R, Flint SJ, San Martín C, de Pablo PJ (2013) Monitoring dynamics of human adenovirus disassembly induced by mechanical fatigue. Sci Rep 3: 1434

    Google Scholar 

  2. Kuznetsov YG, Xiao CA, Sun SY, Raoult D, Rossmann M, McPherson A (2010) Atomic force microscopy investigation of the giant mimivirus. Virology 404:127–137

    Article  CAS  PubMed  Google Scholar 

  3. Roos WH, Radtke K, Kniesmeijer E, Geertsema H, Sodeik B, Wuite GJL (2009) Scaffold expulsion and genome packaging trigger stabilization of herpes simplex virus capsids. Proc Natl Acad Sci USA 106:9673–9678

    Article  CAS  PubMed  Google Scholar 

  4. Kuznetsov YG, Low A, Fan H, McPherson A (2004) Atomic force microscopy investigation of wild-type Moloney murine leukemia virus particles and virus particles lacking the envelope protein. Virology 323:189–196

    Article  CAS  PubMed  Google Scholar 

  5. Carrasco C, Castellanos M, de Pablo PJ, Mateu MG (2008) Manipulation of the mechanical properties of a virus by protein engineering. Proc Natl Acad Sci USA 105:4150–4155

    Article  CAS  PubMed  Google Scholar 

  6. Hernando-Pérez M, Pascual E, Carrasco C, Ionel A, Carrascosa JL, de Pablo PJ (2009) Study of the mechanical properties of bacteriophage T7. Biophys J 96(3):422a–423a

    Google Scholar 

  7. Binnig G, Rohrer H (1982) Scanning tunneling microscopy. Helv Physica Acta 55:726–735

    CAS  Google Scholar 

  8. Chen CJ (1993) Introduction to scanning tunneling microscopy. Oxford University Press, Oxford

    Google Scholar 

  9. Baro AM, Miranda R et al (1985) Determination of surface topography of biological specimens at high-resolution by scanning tunnelling microscopy. Nature 315:253–254

    Article  CAS  PubMed  Google Scholar 

  10. Binnig G, Quate CF, Gerber C (1986) Atomic force microscope. Phys Rev Lett 56:930–933

    Article  PubMed  Google Scholar 

  11. Schmalz G (1929) Uber Glatte und Ebenheit als physikalisches und physiologishes Problem. Verein Deutscher Ingenieure (Oct 12), pp. 1461–1467

    Google Scholar 

  12. Meyer G, Amer NM (1988) Novel optical approach to atomic force microscopy. Appl Phys Lett 53:1045–1047

    Article  Google Scholar 

  13. Sader JE, Chon JWM, Mulvaney P (1999) Calibration of rectangular atomic force microscope cantilevers. Rev Sci Instrum 70:3967–3969

    Article  CAS  Google Scholar 

  14. Butt HJ, Jaschke M (1995) Calculation of thermal noise in atomic-force microscopy. Nanotechnology 6:1–7

    Article  Google Scholar 

  15. Israelachvili J (2002) Intermolecular and surface forces. Academic Press, London

    Google Scholar 

  16. Johnson KL (1985) Contact mechanics. Cambridge University Press, Cambridge

    Book  Google Scholar 

  17. Ohnesorge F, Binnig G (1993) True atomic-resolution by atomic force microscopy through repulsive and attractive forces. Science 260:1451–1456

    Article  CAS  PubMed  Google Scholar 

  18. Giessibl FJ (1995) Atomic-resolution of the silicon (111)-(7x7) surface by atomic-force microscopy. Science 267:68–71

    Article  CAS  PubMed  Google Scholar 

  19. Sugimoto Y, Pou P, Abe M, Jelinek P, Perez R, Morita S, Custance O (2007) Chemical identification of individual surface atoms by atomic force microscopy. Nature 446:64–67

    Article  CAS  PubMed  Google Scholar 

  20. Carpick RW, Ogletree DF, Salmeron M (1997) Lateral stiffness: a new nanomechanical measurement for the determination of shear strengths with friction force microscopy. Appl Phys Lett 70:1548–1550

    Article  CAS  Google Scholar 

  21. Martin Y, Williams CC, Wickramasinghe HK (1987) Atomic force microscope force mapping and profiling on a sub 100-a scale. J Appl Phys 61:4723–4729

    Article  CAS  Google Scholar 

  22. Garcia R, Perez R (2002) Dynamic atomic force microscopy methods. Surf Sci Rep 47:197–301

    Article  CAS  Google Scholar 

  23. Legleiter J, Park M, Cusick B, Kowalewski T (2006) Scanning probe acceleration microscopy (SPAM) in fluids: mapping mechanical properties of surfaces at the nanoscale. Proc Natl Acad Sci 103:4813–4818

    Article  CAS  PubMed  Google Scholar 

  24. Kuznetsov YG, Malkin AJ, Lucas RW, Plomp M, McPherson A (2001) Imaging of viruses by atomic force microscopy. J Gen Virol 82:2025–2034

    CAS  PubMed  Google Scholar 

  25. Miyatani T, Horii M, Rosa A, Fujihira M, Marti O (1997) Mapping of electrical double-layer force between tip and sample surfaces in water with pulsed-force-mode atomic force microscopy. Appl Phys Lett 71:2632–2634

    Article  CAS  Google Scholar 

  26. de Pablo PJ, Colchero J, Gomez-Herrero J, Baro AM (1998) Jumping mode scanning force microscopy. Appl Phys Lett 73:3300–3302

    Article  Google Scholar 

  27. de Pablo PJ, Colchero J, Gomez-Herrero J, Baro AM, Schaefer DM, Howell S, Walsh B, Reifenberger R (1999) Adhesion maps using scanning force microscopy techniques. J Adhes 71:339–356

    Article  Google Scholar 

  28. Ortega-Esteban A, Horcas I, Hernando-Pérez M, Ares P, Pérez-Berná AJ, San Martín C, Carrascosa JL, de Pablo PJ, Gómez-Herrero J (2012) Minimizing tip-sample forces in jumping mode atomic force microscopy in liquid. Ultramicroscopy 114:56–61

    Article  CAS  PubMed  Google Scholar 

  29. Villarrubia JS (1997) Algorithms for scanned probe microscope image simulation, surface reconstruction, and tip estimation. J Res Natl Inst Stan Technol 102:425–454

    Article  Google Scholar 

  30. Marti O, Drake B, Gould S, Hansma PK (1988) Atomic resolution atomic force microscopy of graphite and the native oxide on silicon. J Vac Sci Technol a-Vac Surf Films 6:287–290

    Article  CAS  Google Scholar 

  31. Soler JM, Baro AM, Garcia N, Rohrer H (1986) Interatomic forces in scanning tunneling microscopy—giant corrugations of the graphite surface. Phys Rev Lett 57:444–447

    Article  CAS  PubMed  Google Scholar 

  32. Hansma HG, Sinsheimer RL, Li MQ, Hansma PK (1992) Atomic force microscopy of single-stranded and double-stranded DNA. Nucleic Acids Res 20:3585–3590

    Article  CAS  PubMed  Google Scholar 

  33. Lyubchenko YL, Jacobs BL, Lindsay SM, Stasiak A (1995) Atomic-force microscopy of nucleoprotein complexes. Scanning Microscopy 9:705–727

    CAS  PubMed  Google Scholar 

  34. Dame RT, Wyman C, Goosen N (2003) Insights into the regulation of transcription by scanning force microscopy. Journal of Microscopy-Oxford 212:244–253

    Article  CAS  Google Scholar 

  35. Janicijevic A, Ristic D, Wyman C (2003) The molecular machines of DNA repair: scanning force microscopy analysis of their architecture. Journal of Microscopy-Oxford 212:264–272

    Article  CAS  Google Scholar 

  36. Wagner P, Hegner M, Guntherodt HJ, Semenza G (1995) Formation and in-situ modification of monolayers chemisorbed on ultraflat template-stripped gold surfaces. Langmuir 11:3867–3875

    Article  CAS  Google Scholar 

  37. Muller DJ, Amrein M, Engel A (1997) Adsorption of biological molecules to a solid support for scanning probe microscopy. J Struct Biol 119:172–188

    Article  CAS  PubMed  Google Scholar 

  38. Muller DJ, Janovjak H, Lehto T, Kuerschner L, Anderson K (2002) Observing structure, function and assembly of single proteins by AFM. Prog Biophys Mol Biol 79:1–43

    Article  PubMed  Google Scholar 

  39. Hansma HG, Pietrasanta L (1998) Atomic force microscopy and other scanning probe microscopies. Curr Opin Chem Biol 2:579–584

    Article  CAS  PubMed  Google Scholar 

  40. Horber JKH, Miles MJ (2003) Scanning probe evolution in biology. Science 302:1002–1005

    Article  CAS  PubMed  Google Scholar 

  41. Hinterdorfer P, Dufrene YF (2006) Detection and localization of single molecular recognition events using atomic force microscopy. Nat Meth 3:347–355

    Article  CAS  Google Scholar 

  42. Neuman KC, Nagy A (2008) Single-molecule force spectroscopy: optical tweezers, magnetic tweezers and atomic force microscopy. Nat Meth 5:491–505

    Article  CAS  Google Scholar 

  43. Kirmizis D, Logothetidis S (2010) Atomic force microscopy probing in the measurement of cell mechanics. Int J Nanomed 5:137–145

    Article  Google Scholar 

  44. Kurland NE, Drira Z, Yadavalli VK (2012) Measurement of nanomechanical properties of biomolecules using atomic force microscopy. Micron 43:116–128

    Article  CAS  PubMed  Google Scholar 

  45. Viani MB, Pietrasanta LI, Thompson JB, Chand A, Gebeshuber IC, Kindt JH, Richter M, Hansma HG, Hansma PK (2000) Probing protein-protein interactions in real time. Nat Struct Biol 7:644–647

    Article  CAS  PubMed  Google Scholar 

  46. Moreno-Herrero F, Colchero J, Gomez-Herrero J, Baro AM (2004) Atomic force microscopy contact, tapping, and jumping modes for imaging biological samples in liquids. Phys Rev E 69:031915

    Article  CAS  Google Scholar 

  47. Xu X, Carrasco C, de Pablo PJ, Gomez-Herrero J, Raman A (2008) Unmasking imaging forces on soft biological samples in liquids when using dynamic atomic force microscopy: a case study on viral capsids. Biophys J 95:2520–2528

    Article  CAS  PubMed  Google Scholar 

  48. Kasas S, Thomson NH, Smith BL, Hansma HG, Zhu X, Guthold M, Bustamante C, Kool ET, Kashlev M, Hansma PK (1997) Escherichia coli RNA polymerase activity observed using atomic force microscopy. Biochemistry 36:461–468

    Article  CAS  PubMed  Google Scholar 

  49. Moreno-Herrero F, de Jager M, Dekker NH, Kanaar R, Wyman C, Dekker C (2005) Mesoscale conformational changes in the DNA-repair complex Rad50/Mre11/Nbs1 upon binding DNA. Nature 437:440–443

    Article  CAS  PubMed  Google Scholar 

  50. Kodera N, Yamamoto D, Ishikawa R, Ando T (2010) Video imaging of walking myosin V by high-speed atomic force microscopy. Nature 468:72–76

    Article  CAS  PubMed  Google Scholar 

  51. Plomp M, Rice MK, Wagner EK, McPherson A, Malkin AJ (2002) Rapid visualization at high resolution of pathogens by atomic force microscopy – Structural studies of herpes simplex virus-1. Am J Pathol 160:1959–1966

    Article  CAS  PubMed  Google Scholar 

  52. Kuznetsov YG, McPherson A (2011) Atomic force microscopy in imaging of viruses and virus-infected cells. Microbiol Mol Biol Rev 75:268–285

    Article  CAS  PubMed  Google Scholar 

  53. Ivanovska IL, Miranda R, Carrascosa JL, Wuite GJL, Schmidt CF (2011) Discrete fracture patterns of virus shells reveal mechanical building blocks. Proc Natl Acad Sci USA 108:12611–12616

    Article  CAS  PubMed  Google Scholar 

  54. Castellanos M, Perez R, Carrillo PJP, Pablo PJ, Mateu MG (2012) Mechanical disassembly of single virus particles reveals kinetic intermediates predicted by theory. Biophys J 102:2615–2624

    Article  CAS  PubMed  Google Scholar 

  55. Sieben C, Kappel C, Zhu R, Wozniak A, Rankl C, Hinterdorfer P, Grubmüller H, Herrmann A (2012) Influenza virus binds its host cell using multiple dynamic interactions. Proc Natl Acad Sci USA 109:13626–13631

    Article  CAS  PubMed  Google Scholar 

  56. Xiao C, Kuznetsov YG, Sun S, Hafenstein SL, Kostyuchenko VA, Chipman PR, Suzan-Monti M, Raoult D, McPherson A, Rossmann MG (2009) Structural studies of the giant mimivirus. PLoS Biol 7:958–966

    Article  CAS  Google Scholar 

  57. Vinckier A, Heyvaert I, Dhoore A, Mckittrick T, Vanhaesendonck C, Engelborghs Y, Hellemans L (1995) Immobilizing and imaging microtubules by atomic-force microscopy. Ultramicroscopy 57:337–343

    Article  CAS  PubMed  Google Scholar 

  58. Carrasco C, Luque A, Hernando-Pérez M, Miranda R, Carrascosa JL, Serena PA, de Ridder M, Raman A, Gómez-Herrero J, Schaap IA, Reguera D, de Pablo PJ (2011) Built-in mechanical stress in viral shells. Biophys J 100:1100–1108

    Article  CAS  PubMed  Google Scholar 

  59. Roos WH, Bruinsma R, Wuite GJL (2010) Physical virology. Nat Phys 6:733–743

    Article  CAS  Google Scholar 

  60. Ivanovska IL, de Pablo PJ, Ibarra B, Sgalari G, MacKintosh FC, Carrascosa JL, Schmidt CF, Wuite GJ (2004) Bacteriophage capsids: Tough nanoshells with complex elastic properties. Proc Natl Acad Sci USA 101:7600–7605

    Article  CAS  PubMed  Google Scholar 

  61. Kienberger F, Zhu R, Moser R, Blaas D, Hinterdorfer P (2004) Monitoring RNA release from human rhinovirus by dynamic force microscopy. J Virol 78:3203–3209

    Article  CAS  PubMed  Google Scholar 

  62. Tang JH, Olson N, Jardine PJ, Grimes S, Anderson DL, Baker TS (2008) DNA poised for release in bacteriophage phi 29. Structure 16:935–943

    Article  CAS  PubMed  Google Scholar 

  63. Horcas I, Fernandez R, Gomez-Rodriguez JM, Colchero J, Gomez-Herrero J, Baro AM (2007) WSXM: A software for scanning probe microscopy and a tool for nanotechnology. Rev Sci Instrum 78:013705

    Article  CAS  PubMed  Google Scholar 

  64. Carrasco C, Carreira A, Schaap IAT, Serena PA, Gomez-Herrero J, Mateu MG, de Pablo PJ (2006) DNA-mediated anisotropic mechanical reinforcement of a virus. Proc Natl Acad Sci USA 103:13706–13711

    Article  CAS  PubMed  Google Scholar 

  65. Ando T, Kodera N, Takai E, Maruyama D, Saito K, Toda A (2001) A high-speed atomic force microscope for studying biological macromolecules. Proc Natl Acad Sci USA 98:12468–12472

    Article  CAS  PubMed  Google Scholar 

  66. Melcher J, Carrasco C, Xu X, Carrascosa JL, Gómez-Herrero J, de Pablo PJ, Raman A (2009) Origins of phase contrast in the atomic forces microscopy in liquids. Proc Nat Acad Sci 106:13655–13660

    Article  CAS  PubMed  Google Scholar 

  67. Hoogenboom BW, Hug HJ, Pellmont Y, Martin S, Frederix PLTM, Fotiadis D, Engel A (2006) Quantitative dynamic-mode scanning force microscopy in liquid. Appl Phys Lett 88:193109

    Article  Google Scholar 

  68. Martinez-Martin D, Carrasco C, Hernando-Perez M, de Pablo PJ, Gomez-Herrero J, Perez R, Mateu MG, Carrascosa JL, Kiracofe D, Melcher J, Raman A (2012) Resolving structure and mechanical properties at the nanoscale of viruses with frequency modulation atomic force microscopy. PLoS One 7:e30204

    Article  CAS  PubMed  Google Scholar 

  69. Pérez-Berná AJ, Ortega-Esteban A, Menéndez-Conejero R, Winkler DC, Menéndez M, Steven AC, Flint SJ, de Pablo PJ, San Martín C (2012) The role of capsid maturation on adenovirus priming for sequential uncoating. J Biol Chem 287:31582–31595

    Article  PubMed  Google Scholar 

Further Reading

  • Samorí P (ed) (2006) Scanning force microscopies beyond imaging. Wiley-VCH Weinheim, Germany

    Google Scholar 

  • Baró A, Reifenberger R (2012) Atomic force microscopy in liquid. Wiley-VCH Weinheim, Germany

    Google Scholar 

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Acknowledgements

I thank my students Aida Llauró-Portell, Alvaro Ortega-Esteban and Mercedes Hernando-Pérez, who are carrying out the hardest part of the work. I also want to thank my collaborators Nuria Verdaguer, Mauricio G. Mateu, José López Carrascosa, David Reguera, Julio Gómez-Herrero and Carmen San Martín. I acknowledge funding by grants from the Ministry of Science and Innovation of Spain, PIB2010US-00233, FIS2011-29493, Consolider CSD2010-00024, Comunidad de Madrid No. S2009/MAT-1467, and FIS2011-16090-E.

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Authors and Affiliations

  1. Department of Physics of the Condensed Matter, C03, Facultad de Ciencias, Universidad Autónoma de Madrid, Campus de Cantoblanco, 28049, Madrid, Spain

    Pedro J. de Pablo

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  1. Pedro J. de Pablo
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Correspondence to Pedro J. de Pablo .

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Editors and Affiliations

  1. "Severo Ochoa" (CSIC_UAM), And Dept. of Molecular Biology, Centro de Biología Molecular, Cantoblanco, Madrid, 28049, Madrid, Spain

    Mauricio G. Mateu

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de Pablo, P.J. (2013). Atomic Force Microscopy of Viruses. In: Mateu, M. (eds) Structure and Physics of Viruses. Subcellular Biochemistry, vol 68. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6552-8_8

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