ThT 101: a primer on the use of thioflavin T to investigate amyloid formation

References

• Nietzki R. Chemie der organischen Farbstoffe. Berlin: Springer; 1901.
   Google Scholar
• Basic Yellow 1 [Internet]. dye|World dye variety [published 2012 april; cited 2017 feb 23] Available from: http://www.worlddyevariety.com/basic-dyes/basic-yellow-1.html
   Google Scholar
• Vassar PS, Culling CF. Fluorescent stains, with special reference to amyloid and connective tissues. Arch Pathol. 1959;68:487–498.
   PubMedGoogle Scholar
• Naiki H, Higuchi K, Hosokawa M, et al. Fluorometric determination of amyloid fibrils in vitro using the fluorescent dye, thioflavin T1. Anal Biochem. 1989;177:244–249.
   PubMed Web of Science ®Google Scholar
• Biancalana M, Koide S. Molecular mechanism of Thioflavin-T binding to amyloid fibrils. Biochim Biophys Acta. 2010;1804:1405–1412.
   PubMed Web of Science ®Google Scholar
• LeVine H 3rd. Quantification of beta-sheet amyloid fibril structures with thioflavin T. Methods Enzymol. 1999;309:274–284.
   Google Scholar
• Biancardi A, Biver T, Burgalassi A, et al. Mechanistic aspects of thioflavin-T self-aggregation and DNA binding: evidence for dimer attack on DNA grooves. Phys Chem Chem Phys. 2014;16:20061–20072.
   PubMed Web of Science ®Google Scholar
• Kelenyi G. On the histochemistry of azo group-free thiazole dyes. J Histochem Cytochem. 1967;15:172–180.
   PubMed Web of Science ®Google Scholar
• Ferrari GV, Mallender WD, Inestrosa NC, et al. Thioflavin T is a fluorescent probe of the acetylcholinesterase peripheral site that reveals conformational interactions between the peripheral and acylation sites. J Biol Chem. 2001;276:23282–23287.
   PubMed Web of Science ®Google Scholar
• Buxbaum JN, Linke RP. A molecular history of the amyloidoses. J Molec Biol. 2012;421:142–159.
   PubMed Web of Science ®Google Scholar
• Klunk WE, Wang Y, Huang GF, et al. Uncharged thioflavin-T derivatives bind to amyloid-beta protein with high affinity and readily enter the brain. Life Sci. 2001;69:1471–1484.
   PubMed Web of Science ®Google Scholar
• Maezawa I, Hong HS, Liu R, et al. Congo red and thioflavin-T analogs detect Abeta oligomers. J Neurochem. 2008;104:457–468.
   PubMed Web of Science ®Google Scholar
• Kung MP, Hou C, Zhuang ZP, et al. IMPY: an improved thioflavin-T derivative for in vivo labeling of beta-amyloid plaques. Brain Res. 2002;956:202–210.
   PubMed Web of Science ®Google Scholar
• Sjolander D, Rocken C, Westermark P, et al. Establishing the fluorescent amyloid ligand h-FTAA for studying human tissues with systemic and localized amyloid. Amyloid. 2016;23:98–108.
   PubMed Web of Science ®Google Scholar
• Amytracker™ [Internet]. Solna (SE): Ebba Biotech [cited 2017 Feb 23] Available from: http://www.ebbabiotech.com/collections/amytracker
   Google Scholar
• PROTEOSTAT® Protein aggregation assay [Internet]. Enzo Life Sciences [copyright 2017, cited 2017 Feb 23] Available from: http://www.enzolifesciences.com/ENZ-51023/proteostat-protein-aggregation-assay/
   Google Scholar
• Ferrone F. Analysis of protein aggregation kinetics. Meth Enzymol. 1999;309:256–274.
   PubMed Web of Science ®Google Scholar
• Knowles TP, Vendruscolo M, Dobson CM. The amyloid state and its association with protein misfolding diseases. Nat Rev Mol Cell Biol. 2014;15:384–396.
   PubMed Web of Science ®Google Scholar
• Jarrett JT, Lansbury Jr PT. Seeding “one-dimensional crystallization” of amyloid: a pathogenic mechanism in Alzheimer's disease and scrapie? Cell. 1993;73:1055–1058.
   PubMed Web of Science ®Google Scholar
• Krebs MR, Morozova-Roche LA, Daniel K, et al. Observation of sequence specificity in the seeding of protein amyloid fibrils. Protein Sci. 2004;13:1933–1938.
   PubMed Web of Science ®Google Scholar
• Fauerbach JA, Yushchenko DA, Shahmoradian SH, et al. Supramolecular non-amyloid intermediates in the early stages of α-synuclein aggregation. Biophys J. 2012;102:1127–1136.
   PubMed Web of Science ®Google Scholar
• Sawaya MR, Sambashivan S, Nelson R, et al. Atomic structures of amyloid cross-beta spines reveal varied steric zippers. Nature. 2007;447:453–457.
   PubMed Web of Science ®Google Scholar
• Ban T, Hoshino M, Takahashi S, et al. Direct observation of Abeta amyloid fibril growth and inhibition. J Mol Biol. 2004;344:757–767.
   PubMed Web of Science ®Google Scholar
• Andersen CB, Yagi H, Manno M, et al. Branching in amyloid fibril growth. Biophys J. 2009;96:1529–1536.
   PubMed Web of Science ®Google Scholar
• Andreasen M, Nielsen SB, Runager K, et al. Polymorphic fibrillation of the destabilized fourth fasciclin-1 domain mutant A546T of the Transforming growth factor-beta-induced protein (TGFBIp) occurs through multiple pathways with different oligomeric intermediates. J Biol Chem. 2012;287:34730–34742.
   PubMed Web of Science ®Google Scholar
• Khurana R, Gillespie JR, Talapatra A, et al. Partially folded intermediates as critical precursors of light chain amyloid fibrils and amorphous aggregates. Biochemistry. 2001;40:3525–3535.
   PubMed Web of Science ®Google Scholar
• Morozova-Roche LA, Zurdo J, Spencer A, et al. Amyloid fibril formation and seeding by wild-type human lysozyme and its disease-related mutational variants. J Struct Biol. 2000;130:339–351.
   PubMed Web of Science ®Google Scholar
• Harrison RS, Sharpe PC, Singh Y, et al. Amyloid peptides and proteins in review. Rev Physiol Biochem Pharmacol. 2007;159:1–77.
   PubMed Web of Science ®Google Scholar
• Sunde M, Serpell LC, Bartlam M, et al. Common core structure of amyloid fibrils by synchrotron X-ray diffraction. J Mol Biol. 1997;273:729–739.
   PubMed Web of Science ®Google Scholar
• Khurana R, Ionescu-Zanetti C, Pope M, et al. A general model for amyloid fibril assembly based on morphological studies using atomic force microscopy. Biophys J. 2003;85:1135–1144.
   PubMed Web of Science ®Google Scholar
• Yagi H, Ban T, Morigaki K, et al. Visualization and classification of amyloid beta supramolecular assemblies. Biochemistry. 2007;46:15009–15017.
   PubMed Web of Science ®Google Scholar
• Wu C, Biancalana M, Koide S, et al. Binding modes of thioflavin-T to the single-layer beta-sheet of the peptide self-assembly mimics. J Mol Biol. 2009;394:627–633.
   PubMed Web of Science ®Google Scholar
• Biancalana M, Makabe K, Koide A, et al. Molecular mechanism of thioflavin-T binding to the surface of beta-rich peptide self-assemblies. J Mol Biol. 2009;385:1052–1063.
   PubMed Web of Science ®Google Scholar
• Goldsbury CS, Wirtz S, Muller SA, et al. Studies on the in vitro assembly of a beta 1-40: implications for the search for a beta fibril formation inhibitors. J Struct Biol. 2000;130:217–231.
   PubMed Web of Science ®Google Scholar
• Walsh DM, Hartley DM, Kusumoto Y, et al. Amyloid beta-protein fibrillogenesis. Structure and biological activity of protofibrillar intermediates. J Biol Chem. 1999;274:25945–25952.
   PubMed Web of Science ®Google Scholar
• Habicht G, Haupt C, Friedrich RP, et al. Directed selection of a conformational antibody domain that prevents mature amyloid fibril formation by stabilizing Abeta protofibrils. Proc Natl Acad Sci USA. 2007;104:19232–19237.
   PubMed Web of Science ®Google Scholar
• Gosal WS, Morten IJ, Hewitt EW, et al. Competing pathways determine fibril morphology in the self-assembly of beta2-microglobulin into amyloid. J Mol Biol. 2005;351:850–864.
   PubMed Web of Science ®Google Scholar
• Lorenzen N, Nielsen SB, Buell AK, et al. The role of stable α-synuclein oligomers in the molecular events underlying amyloid formation. J Am Chem Soc. 2014;136:3859–3868.
   PubMed Web of Science ®Google Scholar
• Pires RH, Karsai Á, Saraiva MJ, et al. Distinct annular oligomers captured along the assembly and disassembly pathways of transthyretin amyloid protofibrils. PLoS One. 2012;7:e44992.
   PubMed Web of Science ®Google Scholar
• Zhu M, Han S, Zhou F, et al. Annular oligomeric amyloid intermediates observed by in situ atomic force microscopy. J Biol Chem. 2004;279:24452–24459.
   PubMed Web of Science ®Google Scholar
• Lashuel HA, Petre BM, Wall J, et al. α-Synuclein, especially the Parkinson's disease-associated mutants, forms pore-like annular and tubular protofibrils. J Mol Biol. 2002;322:1089–1102.
   PubMed Web of Science ®Google Scholar
• Atwood CS, Martins RN, Smith MA, et al. Senile plaque composition and posttranslational modification of amyloid-beta peptide and associated proteins. Peptides. 2002;23:1343–1350.
   PubMed Web of Science ®Google Scholar
• Ding TT, Lee SJ, Rochet JC, et al. Annular alpha-synuclein protofibrils are produced when spherical protofibrils are incubated in solution or bound to brain-derived membranes. Biochemistry. 2002;41:10209–10217.
   PubMed Web of Science ®Google Scholar
• Misra P, Kodali R, Chemuru S, et al. Rapid alpha-oligomer formation mediated by the Abeta C terminus initiates an amyloid assembly pathway. Nature Commun. 2016;7:12419.
   PubMed Web of Science ®Google Scholar
• Fandrich M. Oligomeric intermediates in amyloid formation: structure determination and mechanisms of toxicity. J Mol Biol. 2012;421:427–440.
   PubMed Web of Science ®Google Scholar
• LeVine 3rd H. Thioflavine T interaction with synthetic Alzheimer's disease beta-amyloid peptides: detection of amyloid aggregation in solution. Protein Sci. 1993;2:404–410.
   PubMed Web of Science ®Google Scholar
• Come JH, Fraser PE, Lansbury Jr PT. A kinetic model for amyloid formation in the prion diseases: importance of seeding. Proc Natl Acad Sci USA. 1993;90:5959–5963.
   PubMed Web of Science ®Google Scholar
• Hu X, Crick SL, Bu G, et al. Amyloid seeds formed by cellular uptake, concentration, and aggregation of the amyloid-beta peptide. Proc Natl Acad Sci USA. 2009;106:20324–20329.
   PubMed Web of Science ®Google Scholar
• Hayashi H, Kimura N, Yamaguchi H, et al. A seed for Alzheimer amyloid in the brain. J Neurosci. 2004;24:4894–4902.
   PubMed Web of Science ®Google Scholar
• O'Nuallain B, Williams AD, Westermark P, et al. Seeding specificity in amyloid growth induced by heterologous fibrils. J Biol Chem. 2004;279:17490–17499.
   PubMed Web of Science ®Google Scholar
• Teplow DB. Preparation of amyloid beta-protein for structural and functional studies. Meth Enzymol. 2006;413:20–33.
   PubMed Web of Science ®Google Scholar
• Finder VH, Vodopivec I, Nitsch RM, et al. The recombinant amyloid-beta peptide Abeta1-42 aggregates faster and is more neurotoxic than synthetic Abeta1-42. J Mol Biol. 2010;396:9–18.
   PubMed Web of Science ®Google Scholar
• Coin I, Beyermann M, Bienert M. Solid-phase peptide synthesis: from standard procedures to the synthesis of difficult sequences. Nat Protoc. 2007;2:3247–3256.
   PubMed Web of Science ®Google Scholar
• Tickler AK, Clippingdale AB, Wade JD. Amyloid-beta as a “difficult sequence” in solid phase peptide synthesis. Protein Pept Lett. 2004;11:377–384.
   PubMed Web of Science ®Google Scholar
• Applied Biosystems. Cleavage, Deprotection, and Isolation of Peptides after Fmoc Synthesis [Internet]. Thermo Fisher Scientific [revised 1998 May; cited 2017 Jan 23]. Available from: http://tools.thermofisher.com/content/sfs/brochures/cms_040654.pdf
   Google Scholar
• Shen CL, Fitzgerald MC, Murphy RM. Effect of acid predissolution on fibril size and fibril flexibility of synthetic beta-amyloid peptide. Biophys J. 1994;67:1238–1246.
   PubMed Web of Science ®Google Scholar
• Malavolta L, Pinto MR, Cuvero JH, et al. Interpretation of the dissolution of insoluble peptide sequences based on the acid-base properties of the solvent. Protein Sci. 2006;15:1476–1488.
   PubMed Web of Science ®Google Scholar
• Ryan TM, Caine J, Mertens HD, et al. Ammonium hydroxide treatment of Abeta produces an aggregate free solution suitable for biophysical and cell culture characterization. Peer J. 2013;1:e73.
   PubMed Web of Science ®Google Scholar
• Shen CL, Murphy RM. Solvent effects on self-assembly of beta-amyloid peptide. Biophys J. 1995;69:640–651.
   PubMed Web of Science ®Google Scholar
• Terpe K. Overview of tag protein fusions: from molecular and biochemical fundamentals to commercial systems. Appl Microbiol Biotechnol. 2003;60:523–533.
   PubMed Web of Science ®Google Scholar
• Bohm G, Muhr R, Jaenicke R. Quantitative analysis of protein far UV circular dichroism spectra by neural networks. Protein Eng. 1992;5:191–195.
   PubMedGoogle Scholar
• Whitmore L, Wallace BA. DICHROWEB, an online server for protein secondary structure analyses from circular dichroism spectroscopic data. Nucleic Acids Res. 2004;32:W668–W673.
   PubMed Web of Science ®Google Scholar
• Whitmore L, Wallace BA. Protein secondary structure analyses from circular dichroism spectroscopy: methods and reference databases. Biopolymers. 2008;89:392–400.
   PubMed Web of Science ®Google Scholar
• Micsonai A, Wien F, Kernya L, et al. Accurate secondary structure prediction and fold recognition for circular dichroism spectroscopy. Proc Natl Acad Sci USA. 2015;112:E3095–E3103.
   PubMed Web of Science ®Google Scholar
• Nilsson MR. Techniques to study amyloid fibril formation in vitro. Methods. 2004;34:151–160.
   PubMed Web of Science ®Google Scholar
• Schoonenboom NS, Mulder C, Vanderstichele H, et al. Effects of processing and storage conditions on amyloid beta (1-42) and tau concentrations in cerebrospinal fluid: implications for use in clinical practice. Clin Chem. 2005;51:189–195.
   Web of Science ®Google Scholar
• O'Nuallain B, Thakur AK, Williams AD, et al. Kinetics and thermodynamics of amyloid assembly using a high-performance liquid chromatography-based sedimentation assay. Methods Enzymol. 2006;413:34–74.
   PubMed Web of Science ®Google Scholar
• Maji SK, Amsden JJ, Rothschild KJ, et al. Conformational dynamics of amyloid beta-protein assembly probed using intrinsic fluorescence. Biochemistry. 2005;44:13365–13376.
   PubMed Web of Science ®Google Scholar
• Nadal RC, Rigby SE, Viles JH. Amyloid beta-Cu2+ complexes in both monomeric and fibrillar forms do not generate H2O2 catalytically but quench hydroxyl radicals. Biochemistry. 2008;47:11653–11664.
   PubMed Web of Science ®Google Scholar
• Nichols MR, Moss MA, Reed DK, et al. Amyloid-beta protofibrils differ from amyloid-beta aggregates induced in dilute hexafluoroisopropanol in stability and morphology. J Biol Chem. 2005;280:2471–2480.
   PubMed Web of Science ®Google Scholar
• Cohlberg JA, Li J, Uversky VN, et al. Heparin and other glycosaminoglycans stimulate the formation of amyloid fibrils from alpha-synuclein in vitro. Biochemistry. 2002;41:1502–1511.
   PubMed Web of Science ®Google Scholar
• How do I solubilize my peptides? [Internet]. Marlboro (MA): 21st Biochemicals [copyright 2015; cited 2017 Jan 23] Available from: http://www.21stcenturybio.com/custom_services/cust_pep/faqs/solubilize_peptides.shtml
   Google Scholar
• Malavolta L, Pinto MR, Cuvero JH, et al. Interpretation of the dissolution of insoluble peptide sequences based on the acid-base properties of the solvent. Protein Sci. 2006;15:1476–1488.
   PubMed Web of Science ®Google Scholar
• Nichols MR, Moss MA, Reed DK, et al. Amyloid-beta protofibrils differ from amyloid-beta aggregates induced in dilute hexafluoroisopropanol in stability and morphology. J Biol Chem. 2005;280:2471–2480.
   PubMed Web of Science ®Google Scholar
• Broersen K, Jonckheere W, Rozenski J, et al. A standardized and biocompatible preparation of aggregate-free amyloid beta peptide for biophysical and biological studies of Alzheimer's disease. Protein Eng Des Sel. 2011;24:743–750.
   PubMed Web of Science ®Google Scholar
• Jackson M, Mantsch HH. Beware of proteins in DMSO. Biochim Biophys Acta. 1991;1078:231–235.
   PubMed Web of Science ®Google Scholar
• Zagorski MG, Barrow CJ. NMR studies of amyloid.beta.-peptides: proton assignments, secondary structure, and mechanism of an.alpha.-helix.fwdarw.beta.-sheet conversion for a homologous, 28-residue, N-terminal fragment. Biochemistry. 1992;31:5621–5631.
   PubMed Web of Science ®Google Scholar
• Fezoui Y, Teplow DB. Kinetic studies of amyloid beta-protein fibril assembly. Differential effects of alpha-helix stabilization. J Biol Chem. 2002;277:36948–36954.
   PubMed Web of Science ®Google Scholar
• Buck M. Trifluoroethanol and colleagues: cosolvents come of age. Recent studies with peptides and proteins. Q Rev Biophys. 1998;31:297–355.
   PubMed Web of Science ®Google Scholar
• Stine Jr WB, Dahlgren KN, Krafft GA, et al. In vitro characterization of conditions for amyloid-beta peptide oligomerization and fibrillogenesis. J Biol Chem. 2003;278:11612–11622.
   PubMed Web of Science ®Google Scholar
• Lim KH, Collver HH, Le YT, et al. Characterizations of distinct amyloidogenic conformations of the Abeta (1-40) and (1-42) peptides. Biochem Biophys Res Commun. 2007;353:443–449.
   PubMed Web of Science ®Google Scholar
• Lin MS, Chen LY, Tsai HT, et al. Investigation of the mechanism of beta-amyloid fibril formation by kinetic and thermodynamic analyses. Langmuir. 2008;24:5802–5808.
   PubMed Web of Science ®Google Scholar
• Tougu V, Karafin A, Zovo K, et al. Zn(II)- and Cu(II)-induced non-fibrillar aggregates of amyloid-beta (1-42) peptide are transformed to amyloid fibrils, both spontaneously and under the influence of metal chelators. J Neurochem. 2009;110:1784–1795.
   PubMed Web of Science ®Google Scholar
• Khurana R, Coleman C, Ionescu-Zanetti C, et al. Mechanism of thioflavin T binding to amyloid fibrils. J Struct Biol. 2005;151:229–238.
   PubMed Web of Science ®Google Scholar
• Sabate R, Lascu I, Saupe SJ. On the binding of Thioflavin-T to HET-s amyloid fibrils assembled at pH 2. J Struct Biol. 2008;162:387–396.
   PubMed Web of Science ®Google Scholar
• Singh PK, Kumbhakar M, Pal H, Nath S. Ultrafast bond twisting dynamics in amyloid fibril sensor. J Phys Chem B. 2010;114:2541–2546.
   PubMed Web of Science ®Google Scholar
• Lindgren M, Sorgjerd K, Hammarstrom P. Detection and characterization of aggregates, prefibrillar amyloidogenic oligomers, and protofibrils using fluorescence spectroscopy. Biophys J. 2005;88:4200–1422.
   PubMed Web of Science ®Google Scholar
• Kumar S, Singh AK, Krishnamoorthy G, et al. Thioflavin T displays enhanced fluorescence selectively inside anionic micelles and mammalian cells. J Fluoresc. 2008;18:1199–1205.
   PubMed Web of Science ®Google Scholar
• Stsiapura VI, Maskevich AA, Kuzmitsky VA, et al. Thioflavin T as a molecular rotor: fluorescent properties of thioflavin T in solvents with different viscosity. J Phys Chem B. 2008;112:15893–15902.
   PubMed Web of Science ®Google Scholar
• Amdursky N, Gepshtein R, Erez Y, et al. Temperature dependence of the fluorescence properties of thioflavin-T in propanol, a glass-forming liquid. J Phys Chem A. 2011;115:2540–2548.
   PubMed Web of Science ®Google Scholar
• Chatterjee A, Maity B, Seth D. Torsional dynamics of thioflavin T in room-temperature ionic liquids: an effect of heterogeneity of the medium. Chemphyschem. 2013;14:3400–3409.
   PubMed Web of Science ®Google Scholar
• Singh PK, Murudkar S, Mora AK, et al. Ultrafast torsional dynamics of Thioflavin-T in an anionic cyclodextrin cavity. J Photochem Photobiol A Chem 2015;298:40–48.
   Web of Science ®Google Scholar
• Li YY, Jiang XQ, Zhang M, et al. A visual and reversible assay for temperature using thioflavin T-doped lanthanide/nucleotide coordination polymers. Analyst. 2016;141:2347–2350.
   PubMed Web of Science ®Google Scholar
• Hackl EV, Darkwah J, Smith G, et al. Effect of acidic and basic pH on Thioflavin T absorbance and fluorescence. Eur Biophys J. 2015;44:249–261.
   PubMed Web of Science ®Google Scholar
• Fodera V, Groenning M, Vetri V, et al. Thioflavin T hydroxylation at basic pH and its effect on amyloid fibril detection. J Phys Chem B. 2008;112:15174–15181.
   PubMed Web of Science ®Google Scholar
• Hung A, Griffin MD, Howlett GJ, et al. Effects of oxidation, pH and lipids on amyloidogenic peptide structure: implications for fibril formation. Eur Biophys J. 2008;38:99–110.
   PubMed Web of Science ®Google Scholar
• Groenning M. Binding mode of Thioflavin T and other molecular probes in the context of amyloid fibrils-current status. J Chem Biol. 2010;3:1–18.
   PubMedGoogle Scholar
• Kitts CC, Vanden Bout DA. Near-field scanning optical microscopy measurements of fluorescent molecular probes binding to insulin amyloid fibrils. J Phys Chem B. 2009;113:12090–12095.
   PubMed Web of Science ®Google Scholar
• Singh PK, Mora AK, Nath S. Ultrafast fluorescence spectroscopy reveals a dominant weakly-emissive population of fibril bound thioflavin-T. Chem Commun (Camb). 2015;51:14042–14045.
   PubMed Web of Science ®Google Scholar
• Wolfe LS, Calabrese MF, Nath A, et al. Protein-induced photophysical changes to the amyloid indicator dye thioflavin T. Proc Natl Acad Sci USA. 2010;107:16863–16868.
   PubMed Web of Science ®Google Scholar
• Sigma-Aldrich. Thioflavin T (t3516) Product information Sheet. [cited 2016 December 16]. Available from: http://www.sigmaaldrich.com/content/dam/sigma-aldrich/docs/Sigma/Product_Information_Sheet/1/t3516pis.pdf.
   Google Scholar
• abcam. Thioflavin T (ab120751) Product datasheet. [cited 2016 December 16]. Available from: http://www.abcam.com/thioflavin-t-ab120751.html.
   Google Scholar
• Malmos KG, Bjerring M, Jessen CM, et al. How glycosaminoglycans promote fibrillation of salmon calcitonin. J Biol Chem. 2016;291:16849–16862.
   PubMed Web of Science ®Google Scholar
• Kroes-Nijboer A, Lubbersen YS, Venema P, et al. Thioflavin T fluorescence assay for beta-lactoglobulin fibrils hindered by DAPH. J Struct Biol. 2009;165:140–145.
   PubMed Web of Science ®Google Scholar
• Coelho-Cerqueira E, Pinheiro AS, Follmer C. Pitfalls associated with the use of Thioflavin-T to monitor anti-fibrillogenic activity. Bioorg Med Chem Lett. 2014;24:3194–3198.
   PubMed Web of Science ®Google Scholar
• Macchi F, Hoffmann SV, Carlsen M, et al. Mechanical stress affects glucagon fibrillation kinetics and fibril structure. Langmuir. 2011;27:12539–12549.
   PubMed Web of Science ®Google Scholar
• Giehm L, Lorenzen N, Otzen DE. Assays for α-synuclein aggregation. Methods. 2011;53:295–305.
   PubMed Web of Science ®Google Scholar
• Iljina M, Garcia GA, Horrocks MH, et al. Kinetic model of the aggregation of alpha-synuclein provides insights into prion-like spreading. Proc Natl Acad Sci USA. 2016;113:E1206–E1215.
   PubMed Web of Science ®Google Scholar
• Jameson LP, Smith NW, Dzyuba SV. Dye-binding assays for evaluation of the effects of small molecule inhibitors on amyloid (abeta) self-assembly. ACS Chem Neurosci. 2012;3:807–819.
   PubMed Web of Science ®Google Scholar
• Hudson SA, Ecroyd H, Kee TW, et al. The thioflavin T fluorescence assay for amyloid fibril detection can be biased by the presence of exogenous compounds. FEBS J. 2009;276:5960–5972.
   PubMed Web of Science ®Google Scholar
• Meisl G, Kirkegaard JB, Arosio P, et al. Molecular mechanisms of protein aggregation from global fitting of kinetic models. Nat Protoc. 2016;11:252–272.
   PubMed Web of Science ®Google Scholar
• Pedersen JS, Dikov D, Flink JL, et al. The changing face of glucagon fibrillation: structural polymorphism and conformational imprinting. J Mol Biol. 2006;355:501–523.
   PubMed Web of Science ®Google Scholar
• Zhao R, So M, Maat H, et al. Measurement of amyloid formation by turbidity assay-seeing through the cloud. Biophys Rev. 2016;8:445–471.
   PubMedGoogle Scholar
• Fandrich M, Fletcher MA, Dobson CM. Amyloid fibrils from muscle myoglobin. Nature. 2001;410:165–166.
   PubMed Web of Science ®Google Scholar
• Bouchard M, Zurdo J, Nettleton EJ, et al. Formation of insulin amyloid fibrils followed by FTIR simultaneously with CD and electron microscopy. Protein Sci. 2000;9:1960–1967.
   PubMed Web of Science ®Google Scholar
• Krebs MR, Wilkins DK, Chung EW, et al. Formation and seeding of amyloid fibrils from wild-type hen lysozyme and a peptide fragment from the beta-domain. J Mol Biol. 2000;300:541549.
   Web of Science ®Google Scholar
• Chiti F, Bucciantini M, Capanni C, et al. Solution conditions can promote formation of either amyloid protofilaments or mature fibrils from the HypF N-terminal domain. Protein Sci. 2001;10:2541–2547.
   PubMed Web of Science ®Google Scholar
• Nokwe CN, Zacharias M, Yagi H, et al. A residue-specific shift in stability and amyloidogenicity of antibody variable domains. J Biol Chem. 2014;289:26829–26846.
   PubMed Web of Science ®Google Scholar
• Weinreb PH, Zhen W, Poon AW, et al. NACP, a protein implicated in Alzheimer's disease and learning, is natively unfolded. Biochemistry. 1996;35:13709–13714.
   PubMed Web of Science ®Google Scholar
• Andersen CB, Otzen DE, Christiansen G, et al. Glucagon amyloid-like fibril morphology is selected via morphology-dependent growth inhibition. Biochemistry. 2007;46:7314–7324.
   PubMed Web of Science ®Google Scholar
• Chimon S, Shaibat MA, Jones CR, et al. Evidence of fibril-like β-sheet structures in a neurotoxic amyloid intermediate of Alzheimer's β-amyloid. Nat Struct Mol Biol. 2007;14:1157–1164.
   PubMed Web of Science ®Google Scholar
• Pedersen JS, Dikov D, Flink JL, et al. The changing face of glucagon fibrillation: structural polymorphism and conformational imprinting. J Mol Biol. 2006;355:501–523.
   PubMed Web of Science ®Google Scholar
• Nesgaard L, Malmendal A, Hoffmann SV, et al. Characterization of dry globular proteins and protein fibrils by synchrotron radiation vacuum UV circular dichroism. Biopolymers. 2008;89:779–795.
   PubMed Web of Science ®Google Scholar
• Kong J, Yu S. Fourier transform infrared spectroscopic analysis of protein secondary structures. Acta Biochim Biophys Sin (Shanghai). 2007;39:549–559.
   PubMed Web of Science ®Google Scholar
• Zandomeneghi G, Krebs MR, McCammon MG, et al. FTIR reveals structural differences between native beta-sheet proteins and amyloid fibrils. Protein Sci. 2004;13:3314–3321.
   PubMed Web of Science ®Google Scholar
• Shivu B, Seshadri S, Li J, et al. Distinct beta-sheet structure in protein aggregates determined by ATR-FTIR spectroscopy. Biochemistry. 2013;52:5176–5183.
   PubMed Web of Science ®Google Scholar
• Serpell LC, Sunde M, Benson MD, et al. The protofilament substructure of amyloid fibrils. J Mol Biol. 2000;300:1033–1039.
   PubMed Web of Science ®Google Scholar
• Shirahama T, Cohen AS. High-resolution electron microscopic analysis of the amyloid fibril. J Cell Biol. 1967;33:679–708.
   PubMed Web of Science ®Google Scholar
• Fandrich M. On the structural definition of amyloid fibrils and other polypeptide aggregates. Cell Mol Life Sci. 2007;64:2066–2078.
   PubMed Web of Science ®Google Scholar
• Hansma HG, Kim KJ, Laney DE, et al. Properties of biomolecules measured from atomic force microscope images: a review. J Struct Biol. 1997;119:99–108.
   PubMed Web of Science ®Google Scholar
• Stine Jr WB, Snyder SW, Ladror US, et al. The nanometer-scale structure of amyloid-beta visualized by atomic force microscopy. J Protein Chem. 1996;15:193–203.
   PubMedGoogle Scholar
• Anderson VL, Webb WW. Transmission electron microscopy characterization of fluorescently labelled amyloid beta 1-40 and alpha-synuclein aggregates. BMC Biotechnol. 2011;11:125.
   PubMed Web of Science ®Google Scholar