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Near-Field Optical Nanoscopy of Biological Membranes

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Fluorescent Methods to Study Biological Membranes

Part of the book series: Springer Series on Fluorescence ((SS FLUOR,volume 13))

Abstract

The specific organization and distribution of protein receptors and lipids on the cellular plasma membrane play a crucial role for the spatiotemporal control of many different cellular processes. A great deal of novel knowledge in this area is currently being generated thanks to the advent of modern surperresolution optical techniques combined with single-molecule approaches. In this chapter, we focus on near-field nanoscopy, a technique particularly well suited for the study of biological cell surfaces at the nanometer scale. We first describe the general concept of near-field scanning optical microscopy (NSOM) and specifically focus on how NSOM is being exploited to map the spatiotemporal organization of proteins and lipids. Novel routes toward surperresolution using optical nanoantennas and first applications for cell membrane nanoimaging are discussed. The last part of the chapter describes recent technical breakthroughs that enable the application of NSOM in living cells providing detailed dynamic information on diffusion processes occurring at the nanoscale.

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Bibliography

  1. Jares-Erijman EA, Jovin TM (2003) FRET imaging. Nat Biotechnol 21(11):1387–1395

    CAS  Google Scholar 

  2. Varma R, Mayor S (1998) GPI-anchored proteins are organized in submicron domains at the cell surface. Nature 394:798–801

    CAS  Google Scholar 

  3. Sharma P, Varma R, Sarasij RC, Ira GK, Krishnamoorthy G, Rao M, Mayor S (2004) Nanoscale organization of multiple GPI-anchored proteins in living cell membranes. Cell 116:577–589

    CAS  Google Scholar 

  4. Mayor S, Rao M (2004) Rafts: scale-dependent, active lipid organization at the cell surface. Traffic 5:231–240

    CAS  Google Scholar 

  5. Betzig E, Patterson GH, Sougrat R, Lindwasser OW, Olenych S, Bonifacino JS, Davidson MW, Lippincott-Schwartz J, Hess HF (2006) Imaging intracellular fluorescent proteins at nanometer resolution. Science 313:1642–1645

    CAS  Google Scholar 

  6. Hess ST, Girirajan TPK, Mason MD (2006) Ultra-high resolution imaging by fluorescence photoactivation localization microscopy. Biophys J 91:4258–4272

    CAS  Google Scholar 

  7. Rust MJ, Bates M, Zhuang X (2006) Sub-diffraction-limit imaging by stochastic optical reconstruction microscopy (STORM). Nat Methods 3:793–795

    CAS  Google Scholar 

  8. Lillemeier BF, Mörtelmaier MA, Forstner MB, Huppa JB, Groves JT, Davis MM (2010) TCR and Lat are expressed on separate protein islands on T cell membranes and concatenate during activation. Nat Immunol 11:90–96

    CAS  Google Scholar 

  9. Sherman E, Barr V, Manley S, Patterson GH, Balagopalan L, Akpan I, Regan CK, Merrill RK, Sommers CL, Lippincott-Schwartz J, Samelson LE (2011) Functional nanoscale organization of signaling molecules downstream of the T cell antigen receptor. Immunity 35(5):705–720

    CAS  Google Scholar 

  10. Sengupta P, Jovanovic-Talisman T, Skoko D, Renz M, Veatch SL, Lippincott-Schwartz J (2011) Probing protein heterogeneity in the plasma membrane using PALM and pair correlation analysis. Nat Methods 8(11):969–975

    Google Scholar 

  11. Williamson DJ, Owen DM, Rossy J, Magenau A, Wehrmann M, Gooding JJ, Gaus K (2011) Pre-existing clusters of the adaptor Lat do not participate in early T cell signaling events. Nat Immunol 12:655–662

    CAS  Google Scholar 

  12. Sieber JJ, Willig KI, Kutzner C, Gerding-Reimers C, Harke B, Donnert G, Rammner B, Eggeling C, Hell SW, Grubmüller H, Lang T (2007) Anatomy and dynamics of a supramolecular membrane protein cluster. Science 317:1072–1076

    CAS  Google Scholar 

  13. Kellner RR, Baier CJ, Willig KI, Hell SW, Barrantes FJ (2007) Nanoscale organization of nicotinic acetylcholine receptors revealed by stimulated emission depletion microscopy. Neuroscience 144:135–143

    CAS  Google Scholar 

  14. Eggeling C, Ringemann C, Medda R, Schwarzmann G, Sandhoff K, Polyakova S, Belov VN, Hein B, von Middendorff C, Schönle A, Hell SW (2009) Direct observation of the nanoscale dynamics of membrane lipids in a living cell. Nature 457:1159–1162

    CAS  Google Scholar 

  15. Synge EA (1928) A suggested method for extending microscopic resolution into the ultra-microscopic region. Philos Mag 6:356–362.

    CAS  Google Scholar 

  16. Ash EA, Nicholls G (1972) Super-resolution aperture scanning microscope. Nature 237(5357):510–512

    CAS  Google Scholar 

  17. Pohl DW, Denk W, Lanz M (1984) Optical stethoscopy – image recording with resolution lambda/20. Appl Phys Lett 44(7):651–653

    Google Scholar 

  18. Lewis A, Isaacson M, Harootunian A, Muray A (1984) Development of a 500-a spatial-resolution light-microscope. 1. Light is efficiently transmitted through gamma-16 diameter apertures. Ultramicroscopy 13(3):227–231

    Google Scholar 

  19. Peasler MA, Moyer PJ (1996) Near-field optics: theory, instrumentation and applications. Wiley, New York

    Google Scholar 

  20. Betzig E, Trautman JK, Harris TD, Weiner JS, Kostelak RL (1991) Breaking the diffraction barrier: optical microscopy on a nanometric scale. Science 251:1468–1470

    CAS  Google Scholar 

  21. Stockle R, Fokas C, Deckert V, Zenobi R, Sick B, Hecht B, Wild UP (1999) High-quality near-field optical probes by tube etching. Appl Phys Lett 75(2):160–162

    CAS  Google Scholar 

  22. Burgos P, Lu Z, Ianoul A, Hnatovsky C, Viriot M-L, Johnston LJ, Taylor RS (2003) Near-field scanning optical microscopy probes: a comparison of pulled and double-etched bent NSOM probes for fluorescence imaging of biological samples. J Microscopy 211:37–47

    CAS  Google Scholar 

  23. Veerman JA, Otter AM, Kuipers L, van Hulst NF (1998) High definition aperture probes for near-field optical microscopy fabricated by focused ion beam milling. Appl Phys Lett 72:3115–3117

    CAS  Google Scholar 

  24. Betzig E, Finn PL, Weiner JS (1992) Combined shear force and near-field scanning optical microscopy. Appl Phys Lett 60:2484–2486

    CAS  Google Scholar 

  25. Toledo-Crow R, Yang PC, Chen Y, Vaez-Iravani M (1992) Near-field differential scanning optical microscope with atomic force regulation. Appl Phys Lett 60:2957–2959

    CAS  Google Scholar 

  26. Lieberman K, BenAmi N, Lewis A (1996) Fully integrated near-field optical, far-field optical, and normal-force scanned probe microscope. Rev Sci Instrum 67(10):3567–3572

    Google Scholar 

  27. Koopman M, de Bakker BI, Garcia-Parajo MF, van Hulst NF (2003) Shear force imaging of soft samples in liquid using a diving bell concept. Appl Phys Lett 83:5083–5085

    CAS  Google Scholar 

  28. Taylor RS, Vobornik D, Lu Z, Chisholm RA, Johnston LJ (2010) Damping behavior of bent fiber NSOM probes in water. J Appl Phys 107(4):043526

    Google Scholar 

  29. Höppener C, Novotny L (2008) Antenna-based optical imaging of single Ca2+ transmembrane proteins in liquids. Nano Lett 8:642–646

    Google Scholar 

  30. Höppener C, Siebrasse JP, Peters R, Kubitscheck U, Naber A (2005) High-resolution near-field optical imaging of single nuclear pore complexes under physiological conditions. Biophys J 88:3681–3688

    Google Scholar 

  31. Heinzelmann H, Pohl DW (1994) Scanning near-field optical microscopy. Appl Phys A 59(2):89–101

    Google Scholar 

  32. Garcia-Parajo MF, de Bakker BI, Koopman M, Cambi A, de Lange F, Figdor CG, van Hulst NF (2005) Near-field fluorescence microscopy: an optical nanotool to study protein organization at the cell membrane. Nanobiotechnology 1:113–120

    CAS  Google Scholar 

  33. de Lange F, Cambi A, Huijbens R, de Bakker BI, Rensen WHJ, Garcia-Parajo MF, van Hulst NF, Figdor CG (2001) Cell biology beyond the diffraction limit: near-field scanning optical microscopy. J Cell Sci 114:4153–4160

    Google Scholar 

  34. Koopman M, Cambi A, de Bakker BI, Joosten B, Figdor CG, van Hulst NF, Garcia-Parajo MF (2004) Near-field scanning optical microscopy in liquid for high resolution single molecule detection on dendritic cells. FEBS Lett 573:6–10

    CAS  Google Scholar 

  35. Singer SJ, Nicolson GL (1972) The fluid mosaic model of the structure of cell membranes. Science 175(4023):720–731

    CAS  Google Scholar 

  36. Jacobson K, Sheets ED, Simson R (1995) Revisiting the fluid mosaic model of membranes. Science 268(5216):1441–1442

    CAS  Google Scholar 

  37. Maxfield FR (2002) Plasma membrane microdomains. Curr Opin Cell Biol 14:483–487

    CAS  Google Scholar 

  38. Simons M, Friedrichson T, Schulz JB, Pitto M, Masserini M, Kurzchalia TV (1999) Exogenous administration of gangliosides displaces GPI-anchored proteins from lipid microdomains in living cells. Mol Biol Cell 10(10):3187–3196

    CAS  Google Scholar 

  39. Kusumi A, Suzuki KGN (2005) Toward understanding the dynamics of membrane-raft-based molecular interactions. Biochim Biophys Acta 1746(3):234–251

    CAS  Google Scholar 

  40. Douglass AD, Vale RD (2005) Single-molecule microscopy reveals plasma membrane microdomains created by protein-protein networks that exclude or trap signaling molecules in T cells. Cell 121:937–950

    CAS  Google Scholar 

  41. Lingwood D, Simons K (2010) Lipid rafts as a membrane-organizing principle. Science 327:46–50

    CAS  Google Scholar 

  42. Cambi A, Joosten B, Koopman M, de Lange F, Beeren I, Torensma R, Fransen JA, Garcia-Parajo MF, van Leeuwen FN, Figdor CG (2006) Organization of the integrin LFA-1 in nanoclusters regulates its activity. Mol Biol Cell 17:4270–4281

    CAS  Google Scholar 

  43. Cambi A, de Lange F, van Maarseveen NM, Nijhuis M, Joosten B, van Dijk EMHP, de Bakker BI, Fransen JA, Bovee-Geurts PHM, van Leeuwen FN, van Hulst NF, Figdor CG (2004) Microdomains of the C-type lectin DC-SIGN are portals for virus entry into dendritic cells. J Cell Biol 164:145–155

    CAS  Google Scholar 

  44. Mayor S, Pagano RE (2007) Pathways of clathrin-independent endocytosis. Nat Rev Mol Cell Biol 8:603–612

    CAS  Google Scholar 

  45. Mañes S, Viola A (2006) Lipid rafts in lymphocyte activation and migration. Mol Membr Biol 23:59–69

    Google Scholar 

  46. Suzuki KGN, Fujiwara TK, Sanematsu F, Iino R, Edidin MA, Kusumi A (2007) GPI-anchored receptor clusters transiently recruit Lyn and Gα for temporary cluster immobilization and Lyn activation: single-molecule tracking study 1. J Cell Biol 177:717–730

    CAS  Google Scholar 

  47. Lasserre R, Guo X-J, Conchonaud F, Hamon Y, Hawchar O, Bernard A-M, Soudja SMH, Lenne P-F, Rigneault H, Olive D, Bismuth G, Nunès JA, Payrastre B, Marguet D, He H-T (2008) Raft nanodomains contribute to Akt/PKB plasma membrane recruitment and activation. Nat Chem Biol 4:538–547

    CAS  Google Scholar 

  48. Prior IA, Muncke C, Parton RG, Hancock JF (2003) Direct visualization of Ras proteins in spatially distinct cell surface microdomains. J Cell Biol 160:165–170

    CAS  Google Scholar 

  49. Anderson RGW, Jacobson K (2002) A role for lipid shells in targeting proteins to caveolae, rafts, and other lipid domains. Science 296(5574):1821–1825

    CAS  Google Scholar 

  50. Cherukuri A, Carter RH, Brooks S, Bornmann W, Finn R, Dowd CS, Pierce SK (2004) B cell signaling is regulated by induced palmitoylation of CD81. J Biol Chem 279:31973–31982

    CAS  Google Scholar 

  51. Hemler ME (2005) Tetraspanin functions and associated microdomains. Nat Rev Mol Cell Biol 6:801–811

    CAS  Google Scholar 

  52. Maecker HT, Todd SC, Levy S (1997) The tetraspanin superfamily: molecular facilitators. FASEB J 11:428–442

    CAS  Google Scholar 

  53. Berditchevski F (2001) Complexes of tetraspanins with integrins: more than meets the eye. J Cell Sci 114:4143–4151

    CAS  Google Scholar 

  54. Charrin S, le Naour F, Silvie O, Milhiet P-E, Boucheix C, Rubinstein E (2009) Lateral organization of membrane proteins: tetraspanins spin their web. Biochem J 420:133–154

    CAS  Google Scholar 

  55. Yanez-Mo M, Barreiro O, Gordon-Alonso M, Sala-Valdés M, Sanchez-Madrid F (2009) Tetraspanin-enriched microdomains: a functional unit in cell plasma membranes. Trends Cell Biol 19:434–446

    CAS  Google Scholar 

  56. Barreiro O, Zamai M, Yanez-Mo M, Tejera E, López-Romero P, Monk PN, Gratton E, Caiolfa VR, Sanchez-Madrid F (2008) Endothelial adhesion receptors are recruited to adherent leukocytes by inclusion in preformed tetraspanin nanoplatforms. J Cell Biol 183:527–542

    CAS  Google Scholar 

  57. Belanis L, Plowman SJ, Rotblat B, Hancock JF, Kloog Y (2008) Galectin-1 is a novel structural component and a major regulator of H-ras nanoclusters. Mol Biol Cell 19(4):1404–1414

    CAS  Google Scholar 

  58. Nieminen J, Kuno A, Hirabayashi J, Sato S (2007) Visualization of galectin-3 oligomerization on the surface of neutrophils and endothelial cells using fluorescence resonance energy transfer. J Biol Chem 282(2):1374–1383

    CAS  Google Scholar 

  59. Kusumi A, Sako Y (1996) Cell surface organization by the membrane skeleton. Curr Opin Cell Biol 8:566–574

    CAS  Google Scholar 

  60. Kusumi A, Nakada C, Ritchie K, Murase K, Suzuki KGN, Murakoshi H, Kasai RS, Kondo J, Fujiwara TK (2005) Paradigm shift of the plasma membrane concept from the two-dimensional continuum fluid to the partitioned fluid: high-speed single-molecule tracking of membrane molecules. Annu Rev Biophys Biomol Struct 34:351–378

    CAS  Google Scholar 

  61. Andrews NL, Lidke KA, Pfeiffer JR, Burns AR, Wilson BS, Oliver JM, Lidke DS (2008) Actin restricts FcεRI diffusion and facilitates antigen-induced receptor immobilization. Nat Cell Biol 10(8):955–963

    CAS  Google Scholar 

  62. Betzig E, Trautman JK (1992) Near-field optics: microscopy, spectroscopy, and surface modification beyond the diffraction limit. Science 257:189–195

    CAS  Google Scholar 

  63. Enderle T, Ha T, Ogletree DF, Chemla DS, Magowan C, Weiss S (1997) Membrane specific mapping and colocalization of malarial and host skeletal proteins in the Plasmodium falciparum infected erythrocyte by dual-color near-field scanning optical microscopy. Proc Natl Acad Sci 94(2):520–525

    CAS  Google Scholar 

  64. Chen Y, Qin J, Chen Z W (2008) Fluorescence-topographic NSOM directly visualizes peak-valley polarities of GM1/GM3 rafts in cell membrane fluctuations. J Lipid Res 49(10):2268–2275

    CAS  Google Scholar 

  65. Gomez-Mouton C, Abad JL, Mira E, Lacalle RA, Gallardo E, Jimenez-Baranda S, Illa I, Bernad A, Mañes S, Martinez-A C (2001) Segregation of leading-edge and uropod components into specific lipid rafts during T cell polarization. Proc Natl Acad Sci 98(17):9642–9647

    CAS  Google Scholar 

  66. Abulrob A, Lu Z, Brunette E, Pulla D, Stanimirovic D, Johnston LJ (2008) Near-field scanning optical microscopy detects nanoscale glycolipid domains in the plasma membrane. J Microscopy 232:225–234

    CAS  Google Scholar 

  67. van Zanten TS, Gómez J, Manzo C, Cambi A, Buceta J, Reigada R, Garcia-Parajo MF (2010) Direct mapping of nanoscale compositional connectivity on intact cell membranes. Proc Natl Acad Sci 107:15437–15442

    Google Scholar 

  68. Lillemeier BF, Pfeiffer JR, Surviladze Z, Wilson BS, Davis MM (2006) Plasma membrane-associated proteins are clustered into islands attached to the cytoskeleton. Proc Natl Acad Sci 103:18992–18997

    CAS  Google Scholar 

  69. de Bakker BI, de Lange F, Cambi A, Korterik JP, van Dijk EMHP, van Hulst NF, Figdor CG, Garcia-Parajo MF (2007) Nanoscale organization of the pathogen receptor DC-SIGN mapped by single-molecule high-resolution fluorescence microscopy. ChemPhysChem 8:1473–1480

    Google Scholar 

  70. de Bakker BI, Bodná A, van Dijk EMHP, Vámosi G, Damjanovich S, Waldmann TA, van Hulst NF, Jenei A, Garcia-Parajo MF (2008) Nanometer-scale organization of the alpha subunits of the receptors for IL2 and IL15 in human T lymphoma cells. J Cell Sci 121:627–633.

    Google Scholar 

  71. Vobornik D, Rouleau Y, Haley J, Bani-Yaghoub M, Taylor RS, Johnston LJ, Pezacki JP (2009) Nanoscale organization of β2-adrenergic receptor-Venus fusion protein domains on the surface of mammalian cells. Biochem Biophys Res Commun 382:85–90

    CAS  Google Scholar 

  72. Abulrob A, Lu Z, Baumann E, Vobornik D, Taylor RS, Stanimirovic D, Johnston LJ (2010) Nanoscale imaging of epidermal growth factor receptor clustering: effects of inhibitors. J Biol Chem 285:3145–3156

    CAS  Google Scholar 

  73. Chen J, Pei Y, Chen ZW, Cai J (2010) Quantum dot labeling based on near-field optical imaging of CD44 molecules. Micron 41(3):198–202

    CAS  Google Scholar 

  74. Zhong L, Zhang Z, Lu X, Huang D, Chen CY, Wang RC, Chen ZW (2011) NSOM/QD-based fluorescence and topographic image fusion directly reveals nano-spatial peak and valley polarities of CD69 and CD71 activation molecules on cell-membrane fluctuations during T-cell activation. Immunol Lett 140(1–2):44–51

    CAS  Google Scholar 

  75. Zhong L, Zeng G, Lu X, Wang RC, Gong G, Yan L, Huang D, Chen ZW (2009) NSOM/QD-based direct visualization of CD3-induced and CD28-enhanced nanospatial coclustering of TCR and coreceptor in nanodomains in T cell activation. PloS one 4:e5945

    Google Scholar 

  76. Ianoul A, Grant DD, Rouleau Y, Bani-Yaghoub M, Johnston LJ, Pezacki JP (2005) Imaging nanometer domains of beta-adrenergic receptor complexes on the surface of cardiac myocytes. Nat Chem Biol 1:196–202

    CAS  Google Scholar 

  77. van Zanten TS, Cambi A, Koopman M, Joosten B, Figdor CG, Garcia-Parajo MF (2009) Hotspots of GPI-anchored proteins and integrin nanoclusters function as nucleation sites for cell adhesion. Proc Natl Acad Sci 106:18557–18562

    Google Scholar 

  78. Meder D, Moreno MJ, Verkade P, Vaz WLC, Simons K (2006) Phase coexistence and connectivity in the apical membrane of polarized epithelial cells. Proc Natl Acad Sci 103:329–334

    CAS  Google Scholar 

  79. Kenworthy AK, Nichols BJ, Remmert CL, Hendrix GM, Kumar M, Zimmerberg J, Lippincott-Schwartz J (2004) Dynamics of putative raft-associated proteins at the cell surface. J Cell Biol 165:735–746

    CAS  Google Scholar 

  80. Saxton MJ, Jacobson K (1997) Single-particle tracking: applications to membrane dynamics. Annu Rev Biophys Biomol Struct 26:373–399

    CAS  Google Scholar 

  81. Schmidt T, Schütz GJ, Baumgartner W, Gruber HJ, Schindler H (1996) Imaging of single molecule diffusion. Proc Natl Acad Sci 93:2926–2929

    CAS  Google Scholar 

  82. Schwille P, Haupts U, Maiti S, Webb WW (1999) Molecular dynamics in living cells observed by fluorescence correlation spectroscopy with one- and two-photon excitation. Biophys J 77(4):2251–2265

    CAS  Google Scholar 

  83. Kim SA, Heinze KG, Schwille P (2007) Fluorescence correlation spectroscopy in living cells. Nat Methods 4:963–973

    CAS  Google Scholar 

  84. Banks DS, Fradin C (2005) Anomalous diffusion of proteins due to molecular crowding. Biophys J 89:2960–2971

    CAS  Google Scholar 

  85. Vobornik D, Banks DS, Lu Z, Fradin C, Taylor RS, Johnston LJ (2008) Fluorescence correlation spectroscopy with sub-diffraction-limited resolution using near-field optical probes. Appl Phys Lett 93:163904

    Google Scholar 

  86. Herrmann M, Neuberth N, Wissler J, Pérez J, Gradl D, Naber A (2009) Near-field optical study of protein transport kinetics at a single nuclear pore. Nano Lett 9:3330–3336

    CAS  Google Scholar 

  87. Manzo C, van Zanten TS, Garcia-Parajo MF (2011) Nanoscale fluorescence correlation spectroscopy on intact living cell membranes with NSOM probes. Biophys J 100:L8–L10

    CAS  Google Scholar 

  88. Schwille P, Haustein E (2009) Fluorescence correlation spectroscopy an introduction to its concepts and applications. Anal Chem 94(22):1–33

    Google Scholar 

  89. Sahl SJ, Leutenegger M, Hilbert M, Hell SW, Eggeling C (2010) Fast molecular tracking maps nanoscale dynamics of plasma membrane lipids. Proc Natl Acad Sci 107:6829–6834

    CAS  Google Scholar 

  90. Wawrezinieck L, Rigneault H, Marguet D, Lenne P-F (2005) Fluorescence correlation spectroscopy diffusion laws to probe submicron membrane organization. Biophys J 89:4029–4042

    CAS  Google Scholar 

  91. Wenger J, Conchonaud F, Dintinger J, Wawrezinieck L, Ebbesen TW, Rigneault H, Marguet D, Lenne P-F (2007) Diffusion analysis within single nanometric apertures reveals the ultrafine cell membrane organization. Biophys J 92:913–919

    CAS  Google Scholar 

  92. Neumann L, Pang Y, Houyou A, Juan ML, Gordon R, van Hulst NF (2011) Extraordinary optical transmission brightens near-field fiber probe. Nano Lett 11:355–360

    CAS  Google Scholar 

  93. Taminiau TH, Stefani FD, Segerink FB, van Hulst NF (2008) Optical antennas direct single-molecule emission. Nat Photonics 2:234–237

    CAS  Google Scholar 

  94. Kinkhabwala A, Yu Z, Fan S, Avlasevich Y, Müllen K, Moerner WE (2009) Large single-molecule fluorescence enhancements produced by a bowtie nanoantenna. Nat Photonics 3:654–657

    CAS  Google Scholar 

  95. Höppener C, Beams R, Novotny L (2009) Background suppression in near-field optical imaging. Nano Lett 9:903–908

    Google Scholar 

  96. Frey HG, Witt S, Felderer K, Guckenberger R (2004) High-resolution imaging of single fluorescent molecules with the optical near-field of a metal tip. Phys Rev Lett 93:200801

    Google Scholar 

  97. Taminiau TH, Moerland RJ, Segerink FB, Kuipers L, van Hulst NF (2007) λ/4 resonance of an optical monopole antenna probed by single molecule fluorescence. Nano Lett 7:28–33

    CAS  Google Scholar 

  98. Betzig E, Chichester RJ (1993) Single molecules observed by near-field scanning optical microscopy. Science 262:1422–1425

    CAS  Google Scholar 

  99. Bethe HA (1944) Theory of diffraction by small holes. Phys Rev 66:163–182

    Google Scholar 

  100. Bouwkamp CJ (1950) On Bethe’s theory of diffraction by small holes. Philips Res Rep 5:321–332

    Google Scholar 

  101. Garcia-Parajo MF (2008) Optical antennas focus in on biology. Nat Photonics 2:201–203

    CAS  Google Scholar 

  102. Novotny L (2007) Effective wavelength scaling for optical antennas. Phys Rev Lett 98:266802

    Google Scholar 

  103. Thompson RE, Larson DR, Webb WW (2002) Precise nanometer localization analysis for individual fluorescent probes. Biophys J 82:2775–2783

    CAS  Google Scholar 

  104. van Zanten TS, Lopez-Bosque MJ, Garcia-Parajo MF (2010) Imaging individual proteins and nanodomains on intact cell membranes with a probe-based optical antenna. Small 6:270–275

    Google Scholar 

  105. Hrelescu C, Sau TK, Rogach AL, Jäckel F, Laurent G, Douillard L, Charra F (2011) Selective excitation of individual plasmonic hotspots at the tips of single gold nanostars. Nano Lett 11:402–407

    CAS  Google Scholar 

  106. Mivelle M, Ibrahim IA, Baida F, Burr GW, Nedeljkovic D, Charraut D, Rauch JY, Salut R, Grosjean T (2010) Bowtie nano-aperture as interface between near-fields and a single-mode fiber. Opt Express 18(15):15964–15974

    CAS  Google Scholar 

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Correspondence to Maria F. Garcia-Parajo .

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van Zanten, T.S., Manzo, C., Garcia-Parajo, M.F. (2012). Near-Field Optical Nanoscopy of Biological Membranes. In: Mély, Y., Duportail, G. (eds) Fluorescent Methods to Study Biological Membranes. Springer Series on Fluorescence, vol 13. Springer, Berlin, Heidelberg. https://doi.org/10.1007/4243_2012_52

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