Amyloid-Beta 1-42 Binds Preferentially to Nanoscale Electrostatic Domains in Cholesterol-Enriched DOPC Lipid Membrane

Abstract

The plasma membrane is a complex structure, composed primarily of phospholipids and other macromolecules, such as proteins, sterols and steroids. It plays a vital role in cell motility and acts as a barrier for extracellular materials. Amyloid fibrils are linked to multiple neurodegenerative diseases, such as Alzheimer’s. Although fibril plaque formation is associated with biological membranes in vivo, the role of the lipid membrane in fibril formation and toxicity is not well understood. We investigated the interaction of model lipid membranes with Aβ 1-42 peptide. Using Atomic force microscopy, we demonstrated that binding of Aβ 1-42 peptide to DOPC bilayers with 20% cholesterol is non-uniform and resulted in the formation of nanoscale islands loaded with A-beta. We attribute this effect to the presence of electrostatic nanoscale domains induced by cholesterol in the DOPC bilayer. These domains were resolved by AFM imaging of the lipid bilayer and by frequency modulated Kelvin probe force microscopy in the monolayer samples prepared with the Langmuir-Blodgett monolayer technique.