Murugan, N. Arul2; Olsen, Jógvan Magnus Haugaard4; Kongsted, Jacob4; Rinkevicius, Zilvinas2; Aidas, Kestutis3; Ågren, Hans2
1 Department of Physics, Chemistry and Pharmacy, Faculty of Science, SDU2 Division of Theoretical Chemistry and Biology, School of Biotechnology, Royal Institute of Technology3 Vilnius University4 Department of Physics, Chemistry and Pharmacy, Faculty of Science, SDU
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.
Journal of Physical Chemistry Letters, 2013, Vol 4, Issue 1, p. 70-77