Michler’s Hydrol Blue: A Sensitive Probe for Amyloid Fibril Detection

Catherine C. Kitts, Tamás Beke-Somfai, Bengt Nordén

Research output: Contribution to journalArticlepeer-review

48 Scopus citations


Michler's hydrol blue (MHB) is investigated with respect to photophysical properties in varied solvent environment and when bound to insulin and lysozyme fibrils. The MHB chromophore is shown to act like a molecular rotor and bind well to amyloid fibrils, where it exhibits a characteristic red-shift in its excitation spectrum and an increase in the emission quantum yield upon binding. MHB is more sensitive to environmental changes than Thioflavin T (ThT) and furthermore, in contrast to the latter amyloid probe, can differentiate between insulin and lysozyme fibrils by a more red-shifted excitation spectrum for insulin fibrils. To support the experimental observations, time-dependent density functional theory (TDDFT) calculations were performed on MHB at several levels of theory. The predicted changes of spectral properties as a function of the environment are in good agreement with the experimental results. Linear dichroism (LD) is used to determine the orientation of the MHB within the fibrils. It was shown through LD and molecular modeling that MHB aligns itself preferentially parallel with the amyloid fiber at an angle of 14°-22° to the fibril axis and along the grooves of the β-sheet. © 2011 American Chemical Society.
Original languageEnglish (US)
Pages (from-to)3451-3461
Number of pages11
Issue number17
StatePublished - May 3 2011
Externally publishedYes

Bibliographical note

KAUST Repository Item: Exported on 2020-10-01
Acknowledged KAUST grant number(s): KUK-11-008-23
Acknowledgements: B.N. was supported by grants from KAUST. C.C.K. and T.B-S. both. hold a KAUST postdoctoral fellowship.King Abdullah University of Science and Technology (KAUST) (Grant KUK-11-008-23) is gratefully acknowledged. Special thanks to Johan Johansson for assessing the purity of the Michler's hydrol blue sample used in these experiments and to Maria Abrahamsson for help collecting the fluorescence lifetime data. We also thank Per Lincoln for stimulating discussions.
This publication acknowledges KAUST support, but has no KAUST affiliated authors.


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