Aggregation of liposomes induced by the toxic peptides Alzheimer’s Aβs, human amylin and prion (106–126): facilitation by membrane-bound G M1 ganglioside

Abstract

To compare both the peptide molecular self-aggregation and the interaction with membrane lipids of the Alzheimer’s amyloid β (Aβ)40, Aβ42 peptides, and the cytotoxic peptides human amylin and prion (106–126) peptides, we applied a liposome aggregation technology. The kinetics of the changes in the optical density (ΔOD) of liposome suspensions generated by the aggregation of liposomes induced by these peptides, allowed us to comparatively analyze their phospholipid affinity and self-aggregation. The kinetic curves showed an initial nonlinear region where d(ΔOD)/d t followed first order kinetics corresponding to the binding of the peptides to the membrane of the liposome, a linear region where d(ΔOD)/d t was constant, corresponding to the interaction between two membrane-bound peptide molecules, and a final slower increasing nonlinear region that corresponds to nucleation or seeding of aggregation. The analysis of the aggregation curves demonstrated that amylin and prion peptides also showed affinity for the acidic phospholipid phosphatidylserine (PS), as it has previously been shown for the Alzheimer’s Aβ40, Aβ42 peptides. Aβ42 showed the highest, and amylin the lowest, affinity for the liposome membrane. When bound to the membrane of the liposomes, all the peptides preserved the self-aggregation characteristics observed in solution. Aging the Aβ40 and Aβ42 peptide solutions that permit molecular self-aggregation reduced their capacity to induce liposome aggregation. The self-aggregation of membrane-bound prion molecules was several orders of magnitude higher than that observed for the other toxic peptides. Incorporation of the ganglioside G M1 into the membrane of liposomes enhanced the peptide-induced liposome aggregation. Kinetic analysis revealed that this enhancement was due to facilitation of the formation of bridges between membrane-bound peptide molecules, demonstrating that the peptide–membrane interaction and the peptide amyloidogenesis are independent functions performed at separate molecular regions.