1. Department of Chemistry, University of Reading, Whiteknights, Reading RG6 6AD, UK;2. Diamond Light Source, Harwell Science and Innovation Campus, Didcot, Oxon OX11 0DE, UK;3. School of Biological Sciences, Biosciences Building, Crown Street, University of Liverpool, Liverpool L69 7ZB;4. Department of Chemistry and iNANO Interdisciplinary Nanoscience Centre, Aarhus University, DK‐8000 Aarhus, Denmark;5. Department of Biotechnology and Food Engineering and the Russell Berrie Nanotechnology Institute, Technion‐Israel Institute of Technology, Haifa 32000, Israel
Abstract:
The self‐assembly of peptide YYKLVFFC based on a fragment of the amyloid beta (Aβ) peptide, Aβ16–20, KLVFF has been studied in aqueous solution. The peptide is designed with multiple functional residues to examine the interplay between aromatic interactions and charge on the self‐assembly, as well as specific transformations such as the pH‐induced phenol–phenolate transition of the tyrosine residue. Circular dichroism (CD) and Fourier‐transform infrared (FTIR) spectroscopies are used to investigate the conditions for β‐sheet self‐assembly and the role of aromatic interactions in the CD spectrum as a function of pH and concentration. The formation of well‐defined fibrils at pH 4.7 is confirmed by cryo‐TEM (transmission electron microscope) and negative stain TEM. The morphology changes at higher pH, and aggregates of short twisted fibrils are observed at pH 11. Polarized optical microscopy shows birefringence at a low concentration (1 wt.‐%) of YYKLVFFC in aqueous solution, and small‐angle X‐ray scattering was used to probe nematic phase formation in more detail. A pH‐induced transition from nematic to isotropic phases is observed on increasing pH that appears to be correlated to a reduction in aggregate anisotropy upon increasing pH.
