Inhibition of Self-Assembling Peptide Fibrils Formation Using Thioflavin T as a Photosensitizer

Tatiana N. Tikhonova
M.V. Lomonosov Moscow State University, Russia

Anna A. Rubekina
M.V. Lomonosov Moscow State University, Russia

Viktor A. Vorobev
M.V. Lomonosov Moscow State University, Russia

Ekaterina A. Mefodeva
M.V. Lomonosov Moscow State University, Russia

Eugene G. Maksimov
M.V. Lomonosov Moscow State University, Russia

Yuri M. Efremov
Sechenov First Moscow State Medical University, Russia

Maxim E. Darvin
Charité–Universitäts medizin Berlin, Germany

Peter S. Timashev
Sechenov First Moscow State Medical University, Russia

Peter V. Gorelkin
National University of Science and Technology “MISiS”, Moscow, Russia

Alexander S. Erofeev
National University of Science and Technology “MISiS”, Moscow, Russia

Nikolay N. Sysoev
M.V. Lomonosov Moscow State University, Russia

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

hydrogel; peptide self-assembly; photosensitizer; fibrillation; scanning ion conductance microscopy; Thioflavin T; Fmoc-FF

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