Spectroscopic study of protein fibrils

M. Pazderková,1 T. Pazderka,1 M. Shanmugasundaram,2 V. Baumruk,1 I. K. Lednev,2 R. K. Dukor,3 L. A. Nafie4

1Institute of Physics, Faculty of Mathematics and Physics, Charles University in Prague, Ke Karlovu 5, Prague 2, CZ-12116, Czech Republic

2Department of Chemistry, LS 1107, University at Albany, Albany, NY 12222, USA

3BioTools, Inc., 17546 Bee Line Highway (SR 710), Jupiter, FL 33458, USA

4Department of Chemistry, Syracuse University, Syracuse, NY 13244, USA

Understanding of processes of amyloid fibril formation is one of the key tasks in searching for the role of protein structure changes in human neurodegenerative diseases.[1] Many proteins have been found to form amyloid deposits and it has been shown that this might be a general property of a peptide chain.[2] Despite intensive research, the detailed mechanism of fibril formation is still far from clear. Previously, it was discovered that infrared vibrational circular dichroism (VCD) possesses unusual sensitivity to the growth and development of amyloid fibrils, with hen egg lysozyme and bovine insulin as examples.[3] Various homologs of bovine insulin can serve as a model for studies of amyloid fibril formation.

Here we combine vibrational circular dichroism (VCD), atomic force microscopy (AFM) and deep-UV resonance Raman spectroscopy (DUVRR) in an attempt to understand the structure and stability of insulin fibrils under different conditions. Differences in structure and fibril stability for different species and growth conditions will be presented.

1. Dobson, C.M., Nature, 2003, 426, 884-890

2. Dobson, C. M., Trends in Biochemical Sciences, 1999, 24, 329-332.

3. Ma, S., Cao, X., Mak, M., Sadik, A., Walkner, C., Freedman, T. B., Lednev, I. K., Dukor R. K. and Nafie, L. A. Journal of the American Chemical Society, 2007, 129, 12364–12365.

This work was supported by Charles University in Prague (project no. 260092).