Amyloidogenesis of amyloid-β (Aβ) peptides is closely related with pathological neurodegeneration in Alzheimer’s disease. In this study, we investigated the effect of the N-terminal charge-rich region of Aβ40 on its aggregation and interaction with a supported phospholipid bilayer made of 1-palmitoyl-2-oleoylphosphatidylcholine (POPC). Our results show that modulation of the charge properties of the dynamic N-terminal region dramatically influences the intrinsic aggregation propensity of Aβ. Certain mutations of the crucial charged residues in this region significantly interfere with the amyloid fibril formation. Furthermore, we have observed that Aβ–membrane interactions are strongly affected by substitution of charged amino acids at the N-terminal region. Our results demonstrate that the N-terminal charged residues play crucial roles in driving the adsorption as well as the remobilization of the peptide on membrane bilayer, and mediating the rigidity and viscoelasticity properties of the bound Aβ at the membrane interface. The results provide new insight into the Aβ–membrane interactions and binding, which may be critical for understanding membrane-mediated Aβ amyloidogenesis in a cellular environment.

Role of the N-terminal charge-rich region of amyloid-? in amyloidogenesis and interaction with lipid membrane

2019 Spring National Meeting

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