Amyloid Fibril-Induced Structural and Spectral Modifications in the Thioflavin-T Optical Probe.
Motivated by future possibilities to design target molecules for fibrils with diagnostic or therapeutic capability related to amyloidosis diseases, we investigate in this work the dielectric nature of amyloid fibril microenvironments in different binding sites using an optical probe, thioflavin-T (THT), which has been used extensively to stain such fibrils. We study the fibril-environment-induced structural and spectral changes of THT at each binding site and compare the results to the fibril-free situation in aqueous solution. All binding sites are found to show a similar effect with respect to the conformational changes of THT; in the presence of the fibril, its molecular geometry tends to become planarized. However, depending on the dielectric nature of the specific binding site, a red shift, blue shift, or no shift in the absorption spectra of THT is predicted. Interestingly, the experimentally measured red shift in the spectra is seen only when THT binds to one of the core or surface-binding sites. It is found that the dielectric nature of the microenvironment in the fibril is strongly nonhomogeneous.
†Division of Theoretical Chemistry and Biology, School of Biotechnology, Royal Institute of Technology, SE-10691 Stockholm, Sweden.
N Arul
NA
Murugan
‡Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark.
Jógvan Magnus Haugaard
JM
Olsen
‡Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark.
Jacob
J
Kongsted
†Division of Theoretical Chemistry and Biology, School of Biotechnology, Royal Institute of Technology, SE-10691 Stockholm, Sweden.
Zilvinas
Z
Rinkevicius
§Department of General Physics and Spectroscopy, Faculty of Physics, Vilnius University, Sauletekio al. 9, LT-10222 Vilnius, Lithuania.
Kestutis
K
Aidas
†Division of Theoretical Chemistry and Biology, School of Biotechnology, Royal Institute of Technology, SE-10691 Stockholm, Sweden.
Hans
H
Ågren
conformational diseases; fibril-indicator molecules; hybrid QM/MM molecular dynamics; molecular probes; planarization; polarizable electronic embedding