Mechanism of thioflavin T binding to amyloid fibrils

J Struct Biol. 2005 Sep;151(3):229-38. doi: 10.1016/j.jsb.2005.06.006.


Thioflavin T is a benzothiazole dye that exhibits enhanced fluorescence upon binding to amyloid fibrils and is commonly used to diagnose amyloid fibrils, both ex vivo and in vitro. In aqueous solutions, thioflavin T was found to exist as micelles at concentrations commonly used to monitor fibrils by fluorescence assay ( approximately 10-20 microM). Specific conductivity changes were measured at varying concentration of thioflavin T and the critical micellar concentration was calculated to be 4.0+/-0.5 microM. Interestingly, changes in the fluorescence excitation and emission of thioflavin T were also dependent on the micelle formation. The thioflavin T micelles of 3 nm diameter were directly visualized using atomic force microscopy, and bound thioflavin T micelles were observed along the fibril length for representative fibrils. Increasing concentration of thioflavin T above the critical micellar concentration shows increased numbers of micelles bound along the length of the amyloid fibrils. Thioflavin T micelles were disrupted at low pH as observed by atomic force microscopy and fluorescence enhancement upon binding of thioflavin T to amyloid fibrils also reduced by several-fold upon decreasing the pH to below 3. This suggests that positive charge on the thioflavin T molecule has a role in its micelle formation that then bind the amyloid fibrils. Our data suggests that the micelles of thioflavin T bind amyloid fibrils leading to enhancement of fluorescence emission.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amyloid / metabolism*
  • Benzothiazoles
  • Binding Sites
  • Deuterium
  • Fluorescence
  • Fluorescence Polarization
  • Fluorescent Dyes / chemistry
  • Hydrogen-Ion Concentration
  • Micelles
  • Microscopy, Atomic Force
  • Molecular Structure
  • Nuclear Magnetic Resonance, Biomolecular
  • Protein Binding
  • Solutions
  • Spectroscopy, Fourier Transform Infrared
  • Thiazoles / chemistry
  • Thiazoles / metabolism*
  • Water / chemistry


  • Amyloid
  • Benzothiazoles
  • Fluorescent Dyes
  • Micelles
  • Solutions
  • Thiazoles
  • Water
  • thioflavin T
  • Deuterium