Lipids enhance apolipoprotein C-II-derived amyloidogenic peptide oligomerization but inhibit fibril formation

Abstract

We investigated the effect of submicellar lipids on amyloid fibril formation. Thioflavin T fluorescence studies showed that submicellar levels of the short-chain phospholipids, dipentanoylphosphatidylcholine and dihexanoylphosphatidylcholine, strongly inhibited amyloid fibril formation by an 11-residue peptide derived from human apolipoprotein I-II (N60-70). In contrast, sedimentation equilibrium analysis of these peptide-lipid mixtures indicated the presence of soluble oligomeric complexes. To acquire insight into the atomic level influences of these lipids on the initial stages of aggregation of the peptide, we performed molecular dynamics (MD) simulations coupled with umbrella sampling to..