Glutamic acid-rich peptides are crucial to a variety of biological processes, including glutamatergic neurotransmission and immunological defense. Glutamic acid sequences often exhibit unusual organization into β2 -type sheets, where bifurcated H bonds formed between glutamic acid side chains and NH in amide bonds on adjacent β-strands play a paramount role for stabilizing the molecular assembly. Herein, we investigate the self-assembly and supramolecular structure of simplified models consisting of alternating glutamic acid/phenylalanine residues. Small-angle X-ray scattering and atomic force microscopy show that the aggregation pathway is characterized by the formation of small oligomers, followed by coalescence into nanofibrils and nanotapes. Amyloidogenic features are further demonstrated through fiber X-ray diffraction, which reveal molecular packing according to cross-β patterns, where β-strands appear perpendicularly oriented to the long axis of nanofibrils and nanotapes. Nanoscale infrared spectroscopy from individual nanoparticles on dried samples shows a remarkable decrease of β2 -sheet content, accompanied by growth of standard β-sheet fractions, indicating a β2 -to-β1 transition as a consequence of the release of solvent from the interstices of peptide assemblies. Our findings highlight the key role played by water molecules in mediating H-bond formation in β2 -sheets commonly found in amyloidogenic glutamic acid-rich aggregates.
Keywords: AFM-IR; peptide materials; peptide self-assembly; β-amyloid.
© 2019 European Peptide Society and John Wiley & Sons, Ltd.