Hebah Fatafta, Batuhan Kav, Bastian Bundschuh, Jennifer Loschwitz, Birgit Strodel
There is mounting evidence that Alzheimer's disease progression and severity are linked to neuronal membrane damage caused by aggregates of the amyloid-β (Aβ) peptide. However, the detailed mechanism behind the membrane damage is not well understood yet. Recently, the lipid-chaperone hypothesis has been put forward, based on which the formation of complexes between Aβ and free lipids enables an easy insertion of Aβ into membranes. In order to test this hypothesis, we performed numerous all-atom molecular dynamics simulations. The results change considerably once Aβ forms a complex with a POPC cluster composed of three lipid molecules. The hydrophobic interactions between Aβ and the lipid tails cause the peptide to fold into either a helical or a β-sheet structure. These observations provide atomic insight into the disorder-to-order transition that is needed for membrane insertion or amyloid aggregation to proceed.