Aggregation, structure and water permeability of membrane-embedded helical Aβ oligomers.

It is widely recognized that membranes can facilitate the aggregation of amyloid-β (Aβ) peptides, while Aβ can in turn cause membrane damage. Many studies focus on the peptide-membrane interactions of Aβ oligomers with β-rich structures. However, the exact aggregation and toxicity mechanism of the membrane-embedded helical Aβ oligomers remain ambiguous. Herein, the molecular dynamics simulations were performed on membrane-embedded helical Aβ42 peptides. Initiated by eight Aβ42 monomers embedded in a lipid bilayer, the monomers aggregate into oligomers with stable transmembrane helix structures. With the aggregation of peptides, the membrane perturbations caused by Aβ aggregates decrease. The molecular architectures of oligomers were characterized and a helix-rich octamer stabilized by an annular network of hydrogen bonds was observed. The oligomers demonstrate the capability to assist transmembrane water transport. Our study may provide new insights for the investigation of transmembrane Aβ oligomers.