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Studying Protein Misfolding and Aggregation by Fluorescence Spectroscopy

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Reviews in Fluorescence 2015

Part of the book series: Reviews in Fluorescence ((RFLU,volume 8))

Abstract

Protein misfolding leading to aggregation and amyloid fibril formation has been implicated in a variety of neurodegenerative disorders. Under suitably designed in vitro conditions, intermolecular contacts between polypeptide chains mediated by various non-covalent interactions result in the formation of oligomeric species that are eventually sequestered into β-sheet-rich amyloid fibrils. Owing to the inherent heterogeneity and complexity of protein aggregation processes, detection and structural characterization of the early, transiently-populated cytotoxic oligomeric intermediates during the amyloid fibrillation cascade still poses a formidable challenge. Fluorescence spectroscopy is an extremely sensitive multiparametric technique that provides simultaneous information about the conformational- and size changes for both early oligomeric species as well as for the large-sized aggregates. In this review, we emphasize recent and selected examples on the application of various fluorescence spectroscopic techniques in the study of protein aggregation. Additionally, we also summarize the recent results on protein aggregation studies using fluorescence spectroscopy from our laboratory.

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References

  1. Dill KA, Chan HS (1997) From Levinthal to pathways to funnels. Nat Struct Biol 4:10–19

    Article  CAS  PubMed  Google Scholar 

  2. Jahn TR, Radford SE (2008) Folding vs aggregation: polypeptide conformations on competing pathways. Arch Biochem Biophys 469:100–117

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Dobson CM (2006) Protein aggregation and its consequences for human disease. Protein Pept Lett 13:219–227

    Article  CAS  PubMed  Google Scholar 

  4. Uversky VN, Fink AL (2004) Conformational constraints for amyloid fibrillation: the importance of being unfolded. Biochim Biophys Acta 1698:131–153

    Article  CAS  PubMed  Google Scholar 

  5. Morel B, Casares S, Conejero-Lara FA (2006) Single mutation induces amyloid aggregation in the α-spectrin SH3 domain: analysis of the early stages of fibril formation. J Mol Biol 356:453–468

    Article  CAS  PubMed  Google Scholar 

  6. Kumar S, Udgaonkar JB (2010) Mechanisms of amyloid fibril formation by proteins. Curr Sci 98:639–656

    CAS  Google Scholar 

  7. Guijarro JI, Sunde M, Jones JA, Campbell ID, Dobson CM (1998) Amyloid fibril formation by an SH3 domain. Proc Natl Acad Sci U S A 95:4224–4228

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Chiti F, Webster P, Taddei N, Clark A, Stefani M, Ramponi G, Dobson CM (1999) Designing conditions for in vitro formation of amyloid protofilaments and fibrils. Proc Natl Acad Sci U S A 96:3590–3594

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Chiti F, Stefani M, Taddei N, Ramponi G, Dobson CM (2003) Rationalization of the effects of mutations on peptide and protein aggregation rates. Nature 424:805–808

    Article  CAS  PubMed  Google Scholar 

  10. Bucciantini M, Giannoni E, Chiti F, Baroni F, Formigli L, Zurdo J, Taddei N, Ramponi G, Dobson CM, Stefani M (2002) Inherent toxicity of aggregates implies a common mechanism for protein misfolding diseases. Nature 416:507–511

    Article  CAS  PubMed  Google Scholar 

  11. Glabe CG (2008) Structural classification of toxic amyloid oligomers. J Biol Chem 283:29639–29643

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Tycko R (2006) Molecular structure of amyloid fibrils: insights from solid state NMR. Q Rev Biophys 39:1–55

    Article  CAS  PubMed  Google Scholar 

  13. Sivanandam VN, Jayaraman M, Hoop CL, Kodali R, Wetzel R, van der Wel PCA (2011) The aggregation-enhancing Huntingtin N-terminus is helical in amyloid fibrils. J Am Chem Soc 133:4558–4566

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Carulla N, Zhou M, Arimon M, Gairí M, Giralte E, Robinson CV, Dobson CM (2009) Experimental characterization of disordered and ordered aggregates populated during the process of amyloid fibril formation. Proc Natl Acad Sci U S A 106:7828–7833

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Fabian H, Gast K, Laue M, Misselwitz R, Uchanska-Ziegler B, Ziegler A, Naumann D (2008) Early stages of misfolding and association of β 2−microglobulin: insights from infrared spectroscopy and dynamic light scattering. Biochemistry 47:6895–6906

    Article  CAS  PubMed  Google Scholar 

  16. Ma S, Cao X, Mak M, Sadik A, Walkner C, Freedman TB, Lednev IK, Dukor RK, Nafie LA (2007) Vibrational circular dichroism shows unusual sensitivity to protein fibril formation and development in solution. J Am Chem Soc 129:12364–12365

    Article  CAS  PubMed  Google Scholar 

  17. Measey TJ, Schweitzer-Stenner R (2011) Vibrational circular dichroism as a probe of fibrillogenesis: the origin of the anomalous intensity enhancement of amyloid-like fibrils. J Am Chem Soc 133:1066–1076

    Article  CAS  PubMed  Google Scholar 

  18. Sunde M, Blake CCF (1998) From the globular to the fibrous state: protein structure and structural conversion in amyloid formation. Q Rev Biophys 31:1–39

    Article  CAS  PubMed  Google Scholar 

  19. Makin OS, Atkins E, Sikorski P, Johansson J, Serpell LC (2005) Molecular basis for amyloid fibril formation and stability. Proc Natl Acad Sci U S A 102:315–320

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Larson JL, Ko E, Miranker AD (2000) Direct measurement of islet amyloid polypeptide fibrillogenesis by mass spectrometry. Protein Sci 9:427–431

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Smith AM, Jahn TR, Ashcroft AE, Radford SE (2006) Direct observation of oligomeric species formed in the early stages of amyloid fibril formation using electrospray ionisation mass spectrometry. J Mol Biol 364:9–19

    Article  CAS  PubMed  Google Scholar 

  22. Goldsbury C, Baxa U, Simon MN, Steven AC, Engel A, Wall JS, Aebi U, Müller SA (2011) Amyloid structure and assembly: insights from scanning transmission electron microscopy. J Struct Biol 173:1–13

    Article  CAS  PubMed  Google Scholar 

  23. Gosal WS, Myers SL, Radford SE, Thomson NH (2006) Amyloid under the atomic force microscope. Protein Pept Lett 13:261–270

    Article  CAS  PubMed  Google Scholar 

  24. Lakowicz JR (2006) Principles of fluorescence spectroscopy, 3rd edn. Springer, New York

    Book  Google Scholar 

  25. Dusa A, Kaylor J, Edridge S, Bodner N, Hong D-P, Fink AL (2006) Characterization of oligomers during α-synuclein aggregation using intrinsic tryptophan fluorescence. Biochemistry 45:2752–2760

    Article  CAS  PubMed  Google Scholar 

  26. Padrick SB, Miranker AD (2002) Islet amyloid: phase partitioning and secondary nucleation are central to the mechanism of fibrillogenesis. Biochemistry 41:4694–4703

    Article  CAS  PubMed  Google Scholar 

  27. Rolinski OJ, Amaro M, Birch DJS (2010) Early detection of amyloid aggregation using intrinsic fluorescence. Biosens Bioelectron 25:2249–2252

    Article  CAS  PubMed  Google Scholar 

  28. Maji SK, Amsden JJ, Rothschild KJ, Condron MM, Teplow DB (2005) Conformational dynamics of Amyloid β-protein assembly probed using intrinsic fluorescence. Biochemistry 44:13365–13376

    Article  CAS  PubMed  Google Scholar 

  29. van Rooijen BD, van Leijenhorst-Groener KA, Claessens MMAE, Subramaniam V (2009) Tryptophan fluorescence reveals structural features of α-synuclein oligomers. J Mol Biol 394:826–833

    Article  PubMed  Google Scholar 

  30. Jain N, Bhattacharya M, Mukhopadhyay S (2011) Kinetics of surfactant-induced aggregation of lysozyme studied by fluorescence spectroscopy. J Fluoresc 21:615–625

    Article  CAS  PubMed  Google Scholar 

  31. Bhattacharya M, Jain N, Mukhopadhyay S (2011) Insights into the mechanism of aggregation and fibril formation from bovine serum albumin. J Phys Chem B 115:4195–4205

    Article  CAS  PubMed  Google Scholar 

  32. Shukla A, Mukherjee S, Sharma S, Agrawal V, Radhakishan KV, Guptasarma P (2004) A novel UV laser-induced visible blue radiation from protein crystals and aggregates: scattering artifacts or fluorescence transitions of peptide electrons delocalized through hydrogen bonding? Arch Biochem Biophys 428:144–153

    Article  CAS  PubMed  Google Scholar 

  33. del Mercato LL, Pompa PP, Maruccio G, Torre AD, Sabella S, Tamburro AM, Cingolani R, Rinaldi R (2007) Charge transport and intrinsic fluorescence in amyloid-like fibrils. Proc Natl Acad Sci U S A 104:18019–18024

    Article  PubMed  PubMed Central  Google Scholar 

  34. Hawe A, Sutter M, Jiskoot W (2008) Extrinsic fluorescent dyes as tools for protein characterization. Pharm Res 25:1487–1499

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Levine H III (1999) Quantification of β-sheet amyloid fibril structures with thioflavin T. Methods Enzymol 309:274–284

    Article  CAS  PubMed  Google Scholar 

  36. Biancalana M, Koide S (2010) Molecular mechanism of thioflavin-T binding to amyloid fibrils. Biochim Biophys Acta 1804:1405–1412

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Lindgren M, Sörgjerd K, Hammarström P (2005) Detection and characterization of aggregates, prefibrillar amyloidogenic oligomers, and protofibrils using fluorescence spectroscopy. Biophys J 88:4200–4212

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Platt GW, Radford SE (2009) Glimpses of the molecular mechanisms of β2-microglobulin fibril formation in vitro: aggregation on a complex energy landscape. FEBS Lett 583:2623–2629

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Mishra R, Sörgjerd K, Nyström S, Nordigården A, Yu Y-C, Hammarström P (2007) Lysozyme amyloidogenesis is accelerated by specific nicking and fragmentation but decelerated by intact protein binding and conversion. J Mol Biol 366:1029–1044

    Article  CAS  PubMed  Google Scholar 

  40. Hammarström P, Simon R, Nyström S, Konradsson P, Aslund A, Nilsson KPR (2010) A fluorescent pentameric thiophene derivative detects in vitro-formed prefibrillar protein aggregates. Biochemistry 49:6838–6845

    Article  PubMed  Google Scholar 

  41. Lindgren M, Hammarström P (2010) Amyloid oligomers: spectroscopic characterization of amyloidogenic protein states. FEBS J 277:1380–1388

    Article  CAS  PubMed  Google Scholar 

  42. Bjorndahl TC, Zhou G-P, Liu X, Perez-Pineiro R, Semenchenko V, Saleem F, Acharya S, Bujold A, Sobsey CA, Wishart DS (2011) Detailed biophysical characterization of the acid-induced PrPc to PrPβ conversion process. Biochemistry 50:1162–1173

    Article  CAS  PubMed  Google Scholar 

  43. Giurleo JT, He X, Talaga DS (2008) β-lactoglobulin assembles into amyloid through sequential aggregated intermediates. J Mol Biol 381:1332–1348

    Article  CAS  PubMed  Google Scholar 

  44. Bolognesi B, Kumita JR, Barros TP, Esbjorner EK, Luheshi LM, Crowther DC, Wilson MR, Dobson CM, Favrin G, Yerbury JJ (2010) ANS binding reveals common features of cytotoxic amyloid species. ACS Chem Biol 5:735–740

    Article  CAS  PubMed  Google Scholar 

  45. Daniel E, Weber G (1966) Cooperative effects in binding by bovine serum albumin I: the binding of 1-anilino-8-naphthalenesulfonate fluorimetric titrations. Biochemistry 5:1893–1900

    Article  CAS  PubMed  Google Scholar 

  46. Glushko V, Thaler MSR, Karp CD (1981) Pyrene fluorescence fine structure as a polarity probe of hydrophobic regions: behavior in model solvents. Arch Biochem Biophys 210:33–42

    Article  CAS  PubMed  Google Scholar 

  47. Dong DC, Winnik MA (1982) The Py scale of solvent polarities. Solvent effects on the vibronic fine structure of pyrene fluorescence and empirical correlations with the E T and Y values. Photochem Photobiol 35:17–21

    Article  CAS  Google Scholar 

  48. Christensen PA, Pedersen JS, Christiansen G, Otzen DE (2008) Spectroscopic evidence for the existence of an obligate pre-fibrillar oligomer during glucagon fibrillation. FEBS Lett 582:1341–1345

    Article  CAS  PubMed  Google Scholar 

  49. Krishnan R, Lindquist SL (2005) Structural insights into a yeast prion illuminate nucleation and strain diversity. Nature 435:765–772

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Thirunavukkuarasu S, Jares-Erijman EA, Jovin TM (2008) Multiparametric fluorescence detection of early stages in the amyloid protein aggregation of pyrene-labeled α-synuclein. J Mol Biol 378:1064–1073

    Article  CAS  PubMed  Google Scholar 

  51. Mukhopadhyay S, Nayak PK, Udgaonkar JB, Krishnamoorthy G (2006) Characterization of the formation of amyloid protofibrils from barstar by mapping residue-specific fluorescence dynamics. J Mol Biol 358:935–942

    Article  CAS  PubMed  Google Scholar 

  52. Sun Y, Breydo L, Makarava N, Yang Q, Bocharova OV, Baskakov IV (2007) Site-specific conformational studies of prion protein (PrP) amyloid fibrils revealed two cooperative folding domains within amyloid structure. J Biol Chem 282:9090–9097

    Article  CAS  PubMed  Google Scholar 

  53. Yap TL, Pfefferkorn CM, Lee JC (2011) Residue-specific fluorescent probes of α-synuclein: detection of early events at the N- and C-termini during fibril assembly. Biochemistry 50:1963–1965

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Yushchenko DA, Fauerbach JA, Thirunavukkuarasu S, Jares-Erijman EA, Jovin TM (2011) Fluorescent ratiometric MFC probe sensitive to early stages of α-synuclein aggregation. J Am Chem Soc 132:7860–7861

    Article  Google Scholar 

  55. Koo BW, Miranker AD (2005) Contribution of the intrinsic disulfide to the assembly mechanism of islet amyloid. Protein Sci 14:231–239

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Allsop D, Swanson L, Moore S, Davies Y, York A, El-Agnaf OMA, Soutar I (2001) Fluorescence anisotropy: a method for early detection of Alzheimer β-peptide (A-β) aggregation. Biochem Biophys Res Commun 285:58–63

    Article  CAS  PubMed  Google Scholar 

  57. Luk KC, Hyde EG, Trojanowski JQ, Lee VM-Y (2007) Sensitive fluorescence polarization technique for rapid screening of α-synuclein oligomerization/fibrillization inhibitors. Biochemistry 46:12522–12529

    Article  CAS  PubMed  Google Scholar 

  58. Jha A, Udgaonkar JB, Krishnamoorthy G (2009) Characterization of the heterogeneity and specificity of interpolypeptide interactions in amyloid protofibrils by measurement of site-specific fluorescence anisotropy decay kinetics. J Mol Biol 393:735–752

    Article  CAS  PubMed  Google Scholar 

  59. Kayser V, Turton DA, Aggeli A, Beevers A, Reid GD, Beddard GS (2004) Energy migration in novel pH-triggered self-assembled β-sheet ribbons. J Am Chem Soc 126:336–343

    Article  CAS  PubMed  Google Scholar 

  60. Teoh CL, Bekard IB, Asimakis P, Griffin MDW, Ryan TM, Dunstan DE, Howlett GJ (2011) Shear flow induced changes in apolipoprotein C-II conformation and amyloid fibril formation. Biochemistry 50:4046–4057

    Article  CAS  PubMed  Google Scholar 

  61. Nath S, Meuvis J, Hendrix J, Carl SA, Engelborghs Y (2010) Early aggregation steps in α-synuclein as measured by FCS and FRET: evidence for a contagious conformational change. Biophys J 98:1302–1311

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Takahashi T, Kikuchi S, Katada S, Nagai Y, Nishizawa M, Onodera O (2008) Soluble polyglutamine oligomers formed prior to inclusion body formation are cytotoxic. Hum Mol Genet 17:345–356

    Article  CAS  PubMed  Google Scholar 

  63. Schierle GSK, Bertoncini CW, Chan FTS, van der Goot AT, Schwedler S, Skepper J, Schlachter S, van Ham T, Esposito A, Kumita JR, Nollen EAA, Dobson CM, Kaminski CF (2011) A FRET sensor for non-invasive imaging of amyloid formation in vivo. Chem Phys Chem 12:673–680

    Article  Google Scholar 

  64. Mukhopadhyay S, Deniz AA (2007) Biomolecular structure and dynamics using fluorescence from single diffusing molecules. J Fluoresc 17:775–783

    Article  CAS  PubMed  Google Scholar 

  65. Hillger F, Nettels D, Dorsch S, Schuler B (2007) Detection and analysis of protein aggregation with confocal single molecule fluorescence spectroscopy. J Fluoresc 17:759–765

    Article  CAS  PubMed  Google Scholar 

  66. Mukhopadhyay S, Krishnan R, Lemke EA, Lindquist S, Deniz AA (2007) A natively unfolded yeast prion monomer adopts an ensemble of collapsed and rapidly fluctuating structures. Proc Natl Acad Sci U S A 104:2649–2654

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Collins SR, Douglass A, Vale RD, Weissman JS (2004) Mechanism of prion propagation: amyloid growth occurs by monomer addition. PLoS Biol 2(e321):1582–1590

    CAS  Google Scholar 

  68. Orte A, Birkett NR, Clarke RW, Devlin GL, Dobson CM, Klenerman D (2008) Direct characterization of amyloidogenic oligomers by single-molecule fluorescence. Proc Natl Acad Sci U S A 105:14424–14429

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Ding H, Wong PT, Lee EL, Gafni A, Steel DG (2009) Determination of the oligomer size of amyloidogenic protein β-Amyloid(1-40) by single-molecule spectroscopy. Biophys J 97:912–921

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Magde D, Webb WW, Elson E (1972) Thermodynamic fluctuations in a reacting system-measurement by fluorescence correlation spectroscopy. Phys Rev Lett 29:705–708

    Article  CAS  Google Scholar 

  71. Schwille P, Haustein E (2002) Fluorescence correlation spectroscopy: an introduction to its concepts and applications. Biophysics textbook online

    Google Scholar 

  72. Sahoo H, Schwille P (2011) FRET and FCS-friends or foes? Chem Phys Chem 12:532–541

    Article  CAS  PubMed  Google Scholar 

  73. Kolin DL, Wiseman PW (2007) Advances in image correlation spectroscopy: measuring number densities, aggregation states, and dynamics of fluorescently labeled macromolecules in cells. Cell Biochem Biophys 49:141–164

    Article  CAS  PubMed  Google Scholar 

  74. Widengren J, Mets U, Rigler R (1995) Fluorescence correlation spectroscopy of triplet states in solution: a theoretical and experimental study. J Phys Chem 99:13368–13379

    Article  CAS  Google Scholar 

  75. Mütze J, Ohrt T, Schwille P (2011) Fluorescence correlation spectroscopy in vivo. Laser Photonics Rev 5:52–67

    Article  Google Scholar 

  76. Tjernberg LO, Pramanik A, Bjijrling S, Thyberg P, Thyberg J, Nordstedt C, Berndt KD, Terenius L, Rigler R (1999) Amyloid β-peptide polymerization studied using fluorescence correlation spectroscopy. Chem Biol 6:53–62

    Article  CAS  PubMed  Google Scholar 

  77. Kitamura A, Kubota H, Pack C-G, Matsumoto G, Hirayama S, Takahashi Y, Kimura H, Kinjo M, Morimoto RI, Nagata K (2006) Cytosolic chaperonin prevents polyglutamine toxicity with altering the aggregation state. Nat Cell Biol 8:1163–1169

    Article  CAS  PubMed  Google Scholar 

  78. Elbaum-Garfinkle S, Ramlall T, Rhoades E (2010) The role of the lipid bilayer in tau aggregation. Biophys J 98:2722–2730

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Matsumura S, Shinoda K, Yamada M, Yokojima S, Inoue M, Ohnishi T, Shimada T, Kikuchi K, Masui D, Hashimoto S, Sato M, Ito A, Akioka M, Takagi S, Nakamura Y, Nemoto K, Hasegawa Y, Takamoto H, Inoue H, Nakamura S, Nabeshima Y, Teplow DB, Kinjo M, Hoshi M (2011) Two distinct amyloid β Protein (Aβ) assembly pathways leading to oligomers and fibrils identified by combined fluorescence correlation spectroscopy, morphology, and toxicity analyses. J Biol Chem 286:11555–11562

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Sutter M, Oliveira S, Sanders NN, Lucas B, van Hoek A, Hink MA, Visser AJWG, De Smedt SC, Hennink WE, Jiskoot W (2007) Sensitive spectroscopic detection of large and denatured protein aggregates in solution by use of the fluorescent dye Nile red. J Fluoresc 17:181–192

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Sengupta P, Garai K, Balaji J, Periasamy N, Maiti S (2003) Measuring size distribution in highly heterogeneous systems with fluorescence correlation spectroscopy. Biophys J 84:1977–1984

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Vetri V, Ossato G, Militello V, Digman MA, Leone M, Gratton E (2011) Fluctuation methods to study protein aggregation in live cells: concanavalin A oligomers formation. Biophys J 100:774–783

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Takahashi Y, Okamoto Y, Popiel HA, Fujikake N, Toda T, Kinjo M, Nagai Y (2007) Detection of polyglutamine protein oligomers in cells by fluorescence correlation spectroscopy. J Biol Chem 282:24039–24048

    Article  CAS  PubMed  Google Scholar 

  84. Kawai-Noma S, Pack C-G, Kojidani T, Asakawa H, Hiraoka Y, Kinjo M, Haraguchi T, Taguchi H, Hirata A (2010) In vivo evidence for the fibrillar structures of Sup35 prions in yeast cells. J Cell Biol 190:223–231

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Ghosh R, Sharma S, Chattopadhyay K (2009) Effect of arginine on protein aggregation studied by fluorescence correlation spectroscopy and other biophysical methods. Biochemistry 48:1135–1143

    Article  CAS  PubMed  Google Scholar 

  86. Sahoo B, Balaji J, Nag S, Kaushalya SK, Maiti S (2008) Protein aggregation probed by two-photon fluorescence correlation spectroscopy of native tryptophan. J Chem Phys 129:0751031–0751035

    Article  Google Scholar 

  87. Hwang LC, Wohland T (2007) Recent advances in fluorescence cross-correlation spectroscopy. Cell Biochem Biophys 49:1–13

    Article  CAS  PubMed  Google Scholar 

  88. Bieschke J, Schwille P (1998) Aggregation of prion protein investigated by dual-color fluorescence cross-correlation spectroscopy. In: Slavik J (ed) Fluorescence microscopy and fluorescent probes, vol 2. Plenum Press, New York

    Google Scholar 

  89. Bhattacharya M, Jain N, Bhasne K, Kumari V, Mukhopadhyay S (2011) pH-induced conformational isomerization of bovine serum albumin studied by extrinsic and intrinsic protein fluorescence. J Fluoresc 21:1083–1090

    Google Scholar 

  90. Jain N, Bhattacharya M, Mukhopadhyay S (2011) Pyrene excimer formation during polypeptide chain collapse of an amyloidogenic intrinsically disordered protein. Biophys J 101:1720–1729

    Google Scholar 

  91. Ban T, Yamaguchi K, Goto Y (2006) Direct observation of amyloid fibril growth, propagation, and adaptation. Acc Chem Res 39:663–670

    Article  CAS  PubMed  Google Scholar 

  92. Kitts CC, Bout DAV (2009) Near-field scanning optical microscopy measurements of fluorescent molecular probes binding to insulin amyloid fibrils. J Phys Chem B 113:12090–12095

    Article  CAS  PubMed  Google Scholar 

  93. Roberti MJ, Bertoncini CW, Klement R, Jares-Erijman EA, Jovin TM (2007) Fluorescence imaging of amyloid formation in living cells by a functional, tetracysteine-tagged α-synuclein. Nat Methods 4:345–351

    CAS  PubMed  Google Scholar 

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Acknowledgments

We thank IISER Mohali for financial support and the past and present members of the Mukhopadhyay laboratory for their studies on protein aggregation using fluorescence spectroscopy. M.B. thanks the Department of Science and Technology (DST) Women Scientists’ Scheme and S.M. thanks the Council of Scientific and Industrial Research (CSIR), India for research grants.

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  1. Indian Institute of Science Education and Research (IISER) Mohali, S.A.S. Nagar, Sector 81, Mohali, 140306, Punjab, India

    Mily Bhattacharya & Samrat Mukhopadhyay

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  1. Mily Bhattacharya
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  2. Samrat Mukhopadhyay
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Correspondence to Samrat Mukhopadhyay .

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  1. Institute of Fluorescence, University of Maryland Baltimore County Institute of Fluorescence, BALTIMORE, Maryland, USA

    Chris D. Geddes

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Bhattacharya, M., Mukhopadhyay, S. (2016). Studying Protein Misfolding and Aggregation by Fluorescence Spectroscopy. In: Geddes, C. (eds) Reviews in Fluorescence 2015. Reviews in Fluorescence, vol 8. Springer, Cham. https://doi.org/10.1007/978-3-319-24609-3_1

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