The interaction of Aβ42 peptide in monomer, oligomer or fibril forms with sphingomyelin/cholesterol/ganglioside bilayers

A beta 42 peptide binds neuronal membranes and aggregates into plaques that are characteristic of Alzheimer's disease. A beta 42 peptide has been proposed to be generated in membrane (nano) domains in the liquid-ordered phase, ganglioside GM1 being a major facilitator of peptide binding to themembrane. The peptide exists in solution in various degrees of aggregation, either monomers, oligomers or fibrils, of which oligomers appear to be particularly toxic. The present study reports on the binding of A beta 42 peptide, in monomer, oligomer or fibril form, to model membranes (lipid vesicles or monolayers), composed of sphingomyelin and cholesterol in equimolar ratios, to which 1-5 mol% of different gangliosides were incorporated. Thermodynamic binding parameters obtained from calorimetric data indicate a strong tendency to bind the membrane (Delta G approximate to 7 kcal/mol peptide), in a process dominated in most cases by the increase in entropy. Delta G was virtually invariant with the ganglioside species and the aggregation state of the peptide. The Langmuir balance demonstrated the capacity of all peptide preparations to become inserted in lipid monolayers of any composition and initial pi in the range 10-30mN/m, although fibrils were less capable to do so than oligomers or monomers, their maximum initial pi being approximate to 25 mN/m. (C) 2020 Published by Elsevier B.V.

Automated summary

The β42 peptide, a component of Alzheimer's disease plaques, binds neuronal membranes and tends to aggregate in various states, with ganglioside GM1 being a major facilitator. Thermodynamic data suggests a strong tendency for peptide-membrane binding, mainly driven by entropy. The Langmuir balance demonstrated the ability of all peptide preparations to insert into lipid monolayers, with fibrils having lower capability compared to oligomers or monomers.