Mixed Phospholipid Vesicles Catalytically Inhibit and Reverse Amyloid Fibril Formation

While many approaches to reduce fibrillation of amyloid-β (Aβ) have been aimed at slowing fibril formation, the degradation of fibrils remains challenging. We provide insight into fibril degradation as well as the inhibition of fiber formation by lipid vesicles composed of 1,2-dioleoyl-sn-glycero-3-phosphocholine and 1,2-dioleoyl-sn-glycero-3-phospho-(1′-rac-glycerol). In the presence of vesicles with the optimal lipid composition, fibril formation was inhibited up to 76%. Additionally, by tuning the lipid composition, mature fibril content decreased up to 74% and the β-sheet content of Aβ was significantly reduced. The reduction in fibril and β-sheet content was consistent with a decrease in fibril diameter and could be attributed to the chaperone-like activity of the mixed vesicles. While demonstrating this remarkable activity, our findings present new evidence that lipid composition has a significant effect on the strength of the interaction between lipid bilayers and Aβ peptides/fibrils. This understanding has intriguing therapeutic implications in treating protein misfolding diseases.