Hide
Show all
Inhibition of Self-Assembling Peptide Fibrils Formation Using Thioflavin T as a Photosensitizer
Evgeny A. Shirshin
(Login required)
M.V. Lomonosov Moscow State University, Russia
Paper #3572 received 16 Dec 2022; revised manuscript received 20 Dec 2022; accepted for publication 21 Dec 2022; published online 3 Feb 2023.
DOI: 10.18287/JBPE23.09.010304
Abstract
Misfolded proteins produce fibrillar aggregates, which contain β-sheet higher order structures. The oligomers, protofibrils, and fibrils generated during protein aggregation process are cytotoxic and can cause various neurodegenerative diseases. Recently the photo-active materials, the photosensitizers, have attracted increased attention in the study and treatment of amyloid-related diseases. Here, we studied the photodynamic effect of the amyloid-specific fluorescence dye Thioflavin T on the formation of self-assembled peptide hydrogel. It was demonstrated that the gelation process under irradiation inhibits significantly, at that the structural and mechanical properties of mature fibrils change notably suggesting that ThT could be regarded as a theranostic probe. The developed peptide model allows for quantification of the photodynamic agent’s efficiency in preventing aggregation, thus paving the way for a high-throughput test system for screening of light-responsive theranostic agents.
Keywords
References
1. C. Soto, S. Pritzkow, “Protein misfolding, aggregation, and conformational strains in neurodegenerative diseases,” Nature Neuroscience 21(10), 1332–1340 (2018).
2. A. B. Diack, J. D. Alibhai, R. Barron, B. Bradford, P. Piccardo, and J. C. Manson, “Insights into mechanisms of chronic neurodegeneration,” International Journal of Molecular Sciences 17(1), 82 (2016).
3. C. Peng, J. Q. Trojanowski, and V. M. Y. Lee, “Protein transmission in neurodegenerative disease,” Nature Reviews Neurology 16(4), 199–212 (2020).
4. C. Di Scala, N. Yahi, S. Boutemeur, A. Flores, L. Rodriguez, H. Chahinian, and J. Fantini, “Common molecular mechanism of amyloid pore formation by Alzheimer’s β-amyloid peptide and α-synuclein,” Scientific Reports 6(1), 28781 (2016).
5. C. A. Ross, M. A. Poirier, “What is the role of protein aggregation in neurodegeneration?” Nature Reviews Molecular Cell Biology 6(11), 891–898 (2005).
6. F. J. Bäuerlein, R. Fernández-Busnadiego, and W. Baumeister, “Investigating the structure of neurotoxic protein aggregates inside cells,” Trends in Cell Biology 30(12), 951–966 (2020).
7. P. Velander, L. Wu, F. Henderson, S. Zhang, D. R. Bevan, and B. Xu, “Natural product-based amyloid inhibitors,” Biochemical Pharmacology 139, 40–55 (2017).
8. R. Liu, R. Su, M. Liang, R. Huang, M. Wang, W. Qi, and Z. He, “Physicochemical strategies for inhibition of amyloid fibril formation: an overview of recent advances,” Current Medicinal Chemistry 19(24), 4157–4174 (2012).
9. B. I. Lee, Y. J. Chung, and C. B. Park, “Photosensitizing materials and platforms for light-triggered modulation of Alzheimer's β-amyloid self-assembly,” Biomaterials 190, 121–132 (2019).
10. B. S. Dash, S. Das, and J. P. Chen, “Photosensitizer-functionalized nanocomposites for light-activated cancer theranostics,” International Journal of Molecular Sciences 22(13), 6658 (2021).
11. K. Kannan, D. Radhika, K. K. Sadasivuni, K. R. Reddy, and A. V. Raghu, “Nanostructured metal oxides and its hybrids for photocatalytic and biomedical applications,” Advances in Colloid and Interface Science 281, 102178 (2020).
12. J. S. Lee, B. I. Lee, and C. B. Park, “Photo-induced inhibition of Alzheimer's β-amyloid aggregation in vitro by rose bengal,” Biomaterials 38, 43–49 (2015).
13. M. Oz, D. E. Lorke, M. Hasan, and G. A. Petroianu, “Cellular and molecular actions of Methylene Blue in the nervous system,” Medicinal Research Reviews 31(1), 93–117 (2011).
14. B. I. Lee, Y. S. Suh, Y. J. Chung, K. Yu, and C. B. Park, “Shedding light on Alzheimer’s β-amyloidosis: photosensitized methylene blue inhibits self-assembly of β-amyloid peptides and disintegrates their aggregates,” Scientific Reports 7(1), 7523 (2017).
15. N. R. Rovnyagina, G. S. Budylin, Y. G. Vainer, T. N.Tikhonova, S. L. Vasin, A. A. Yakovlev, V. O. Kompanets, S. V. Chekalin, A. V. Priezzhev, and E. A. Shirshin, “Fluorescence lifetime and intensity of thioflavin T as reporters of different fibrillation stages: Insights obtained from fluorescence up-conversion and particle size distribution measurements,” International Journal of Molecular Sciences 21(17), 6169 (2020).
16. B. Frieg, L. Gremer, H. Heise, D. Willbold, and H. Gohlke, “Binding modes of thioflavin T and Congo red to the fibril structure of amyloid-β (1–42),” Chemical Communications 56(55), 7589–7592 (2020).
17. D. Ozawa, Y. Kaji, H. Yagi, K. Sakurai, T. Kawakami, H. Naiki, and Y. Goto, “Destruction of amyloid fibrils of keratoepithelin peptides by laser irradiation coupled with amyloid-specific thioflavin T,” Journal of Biological Chemistry 286(12), 10856–10863 (2011).
18. V. I. Stsiapura, A. A. Maskevich, V. A. Kuzmitsky, V. N. Uversky, I. M. Kuznetsova, and K. K. Turoverov, “Thioflavin T as a molecular rotor: fluorescent properties of thioflavin T in solvents with different viscosity,” The Journal of Physical Chemistry B 112(49), 15893–15902 (2008).
19. F. Y. Khusbu, X. Zhou, H. Chen, C. Ma, and K. Wang, “Thioflavin T as a fluorescence probe for biosensing applications,” Trends in Analytical Chemistry 109, 1–18 (2018).
20. V. I. Stsiapura, A. A. Maskevich, S. A. Tikhomirov, and O. V. Buganov, “Charge transfer process determines ultrafast excited state deactivation of thioflavin T in low-viscosity solvents,” The Journal of Physical Chemistry A 114(32), 8345–8350 (2010).
21. N. Amdursky, Y. Erez, and D. Huppert, “Molecular rotors: what lies behind the high sensitivity of the thioflavin-T fluorescent marker,” Accounts of Chemical Research 45(9), 1548–1557 (2012).
22. A. M. Smith, R. J. Williams, C. Tang, P. Coppo, R. F. Collins, M. L. Turner, A. Saiani, and R. V. Ulijn, “Fmoc-diphenylalanine self assembles to a hydrogel via a novel architecture based on π–π interlocked β-sheets,” Advanced Materials 20(1), 37–41 (2008).
23. C. Diaferia, M. Ghosh, T. Sibillano, E. Gallo, M. Stornaiuolo, C. Giannini, G. Morelli, L. Adler-Abramovich, and A. Accardo, “Fmoc-FF and hexapeptide-based multicomponent hydrogels as scaffold materials,” Soft Matter 15(3), 487–496 (2019).
24. R. Orbach, I. Mironi-Harpaz, L. Adler-Abramovich, E. Mossou, E. P. Mitchell, V. T. Forsyth, E. Gazit, and D. Seliktar, “The rheological and structural properties of Fmoc-peptide-based hydrogels: the effect of aromatic molecular architecture on self-assembly and physical characteristics,” Langmuir 28(4), 2015–2022 (2012).
25. E. Rosa, C. Diaferia, E. Gianolio, T. Sibillano, E. Gallo, G. Smaldone, M. Stornaiuolo, C. Giannini, G. Morelli, and A. Accardo, “Multicomponent Hydrogel Matrices of Fmoc-FF and Cationic Peptides for Application in Tissue Engineering,” Macromolecular Bioscience 22(7), 2200128 (2022).
26. T. N. Tikhonova, N. R. Rovnyagina, Z. A. Arnon, B. P. Yakimov, Y. M. Efremov, D. Cohen-Gerassi, M. Halperin-Sternfeld, N. V. Kosheleva, V. P. Drachev, A. A. Svistunov, P. S. Timashev, L. Adler-Abramovich, and E. A. Shirshin, “Mechanical Enhancement and Kinetics Regulation of Fmoc-Diphenylalanine Hydrogels by Thioflavin T,” Angewandte Chemie International Edition 60(48), 25339–25345 (2021).
27. K. Lundmark, G. T. Westermark, A. Olsén, and P. Westermark, “Protein fibrils in nature can enhance amyloid protein A amyloidosis in mice: Cross-seeding as a disease mechanism,” Proceedings of the National Academy of Sciences 102(17), 6098–6102 (2005).
28. C. Li, J. Adamcik, and R. Mezzenga, “Biodegradable nanocomposites of amyloid fibrils and graphene with shape-memory and enzyme-sensing properties,” Nature Nanotechnology 7(7), 421–427 (2012).
29. V. Basavalingappa, T. Guterman, Y. Tang, S. Nir, J. Lei, P. Chakraborty, L. Schnaider, M. Reches, G. Wei, and E. Gazit, “Expanding the functional scope of the fmoc-diphenylalanine hydrogelator by introducing a rigidifying and chemically active urea backbone modification,” Advanced Science 6(12), 1900218 (2019).
30. J. Raeburn, G. Pont, L. Chen, Y. Cesbron, R. Lévy, and D. J. Adams, “Fmoc-diphenylalanine hydrogels: understanding the variability in reported mechanical properties,” Soft Matter 8(4), 1168–1174 (2012).
31. A. I. Sulatskaya, A. V. Lavysh, A. A. Maskevich, I. M. Kuznetsova, and K. K. Turoverov, “Thioflavin T fluoresces as excimer in highly concentrated aqueous solutions and as monomer being incorporated in amyloid fibrils,” Scientific Reports 7(1), 2146 (2017).
32. A. Page, D. Perry, and P. R. Unwin, “Multifunctional scanning ion conductance microscopy,” Proceedings of the Royal Society A: Mathematical, Physical and Engineering Sciences 473(2200), 20160889 (2017).
33. B. Yakimov, A. Gayer, E. Maksimov, E. Mamonov, A. Maydykovsky, T. Murzina, V. Fadeev, and E. Shirshin, “Fluorescence saturation imaging microscopy: molecular fingerprinting in living cells using two-photon absorption cross section as a contrast mechanism,” Optics Letters 47(17), 4455–4458 (2022).
34. S. Kundu, C. Banerjee, and N. Sarkar, “Inhibiting the fibrillation of serum albumin proteins in the presence of surface active ionic liquids (SAILs) at low pH: spectroscopic and microscopic study,” The Journal of Physical Chemistry B 121(32), 7550–7560 (2017).
35. V. S. Kolmogorov, A. S. Erofeev, E. Woodcock, Y. M. Efremov, A. P. Iakovlev, N. A. Savin, A. V. Alova, S. V. Lavrushkina, I. I. Kireev, A. O. Prelovskaya, E. V. Sviderskaya, D. Scaini, N. L. Klyachko, P. S. Timashev, Y. Takahashi, S. V. Salikhov, Y. N. Parkhomenko, A. G. Majouga, C. R. W. Edwards, P. Novak, Y. E. Korchev, and P. V. Gorelkin, “Mapping mechanical properties of living cells at nanoscale using intrinsic nanopipette–sample force interactions,” Nanoscale 13(13), 6558–6568 (2021).
36. Y. Zhang, Y. Takahashi, S. P. Hong, F. Liu, J. Bednarska, P. S. Goff, P. Novak, A. Shevchuk, S. Gopal, I. Barozzi, L. Magnani, H. Sakai, Y. Suguru, T. Fujii, A. Erofeev, P. Gorelkin, A. Majouga, D. J. Weiss, C. Edwards, A. P. Ivanov, D. Klenerman, E. V. Sviderskaya, J. B. Edel, and Y. Korchev, “High-resolution label-free 3D mapping of extracellular pH of single living cells,” Nature Communications 10(1), 5610 (2019).
37. Y. Takahashi, A. I. Shevchuk, P. Novak, Y. Murakami, H. Shiku, Y. E. Korchev, and T. Matsue, “Simultaneous noncontact topography and electrochemical imaging by SECM/SICM featuring ion current feedback regulation,” Journal of the American Chemical Society 132(29), 10118–10126 (2010).
38. D. Ozawa, H. Yagi, T. Ban, A. Kameda, T. Kawakami, H. Naiki, and Y. Goto, “Destruction of amyloid fibrils of a β2-microglobulin fragment by laser beam irradiation,” Journal of Biological Chemistry 284(2), 1009–1017 (2009).
39. H. Yagi, D. Ozawa, K. Sakurai, T. Kawakami, H, Kuyama, O. Nishimura, T. Shimanouchi, R. Kuboi, H. Nauki, and Y. Goto, “Laser-induced propagation and destruction of amyloid β fibrils,” Journal of Biological Chemistry 285(25), 19660–19667 (2010).
40. M. Ahn, B. I. Lee, S. Chia, J. Habchi, J. R. Kumita, M. Vendruscolo, C. Dobson, and C. B. Park, “Chemical and mechanistic analysis of photodynamic inhibition of Alzheimer’s β-amyloid aggregation,” Chemical Communications 55(8), 1152–1155 (2019).
© 2014-2023 Samara National Research University. All Rights Reserved.
Public Media Certificate (RUS). 12+