title: Self-assembly of a modified amyloid peptide fragment: pH-responsiveness and nematic phase formation.
abstract: The self-assembly of peptide YYKLVFFC based on a fragment of the amyloid beta (A beta) peptide, A beta 16-20, 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 beta-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.
authors.affiliation: Department of Chemistry, University of Reading, Whiteknights, Reading RG6 6AD, UK. i.w.hamley@reading.ac.uk
authors.forename: Ian W
authors.initials: IW
authors.lastname: Hamley
authors.forename: Valeria
authors.initials: V
authors.lastname: Castelletto
authors.forename: Claire
authors.initials: C
authors.lastname: Moulton
authors.forename: Daniel
authors.initials: D
authors.lastname: Myatt
authors.forename: Giuliano
authors.initials: G
authors.lastname: Siligardi
authors.forename: Cristiano L P
authors.initials: CL
authors.lastname: Oliveira
authors.forename: Jan Skov
authors.initials: JS
authors.lastname: Pedersen
authors.forename: Inbal
authors.initials: I
authors.lastname: Abutbul
authors.forename: Dganit
authors.initials: D
authors.lastname: Danino
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry*; D002942:Circular Dichroism; D020285:Cryoelectron Microscopy; D006863:Hydrogen-Ion Concentration; D013058:Mass Spectrometry; D010446:Peptide Fragments / Q000096:biosynthesis* / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D014961:X-Ray Diffraction
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments