Insertion of Alzheimer’s A β40 Peptide into Lipid Monolayers

Abstract

The amyloid beta (A β) peptide is the major component found in the amyloid deposits in the brains of Alzheimer’s disease patients. In vitro studies have demonstrated that the aggregation of A β can take place at three orders of magnitude lower concentrations in the presence of phospholipid molecules compared to bulk peptide studies, suggesting that membrane lipids may mediate A β toxicity. To understand the interaction of A β with lipid membranes, we have examined A β40 with anionic dipalmitoylphosphatidylglycerol (DPPG), zwitterionic dipalmitoylphosphatidylcholine (DPPC), and cationic dipalmitoyltrimethylammonium propane (DPTAP) monolayers under different subphase conditions. We have used a constant surface pressure insertion assay to assess the degree of peptide insertion into the lipids. Simultaneously, we monitored the surface morphology of the monolayers with fluorescence microscopy. We have also performed dual-probe fluorescence measurements where both the peptide and lipid are tagged with chromophores. Isotherm measurements show that A β inserts into both DPTAP and DPPG monolayers under physiologically relevant conditions. Insertion into DPPC occurs at lipid densities below that found in a bilayer. The level of insertion is inversely proportional to the lipid packing density. Our results indicate that lipids need not be anionic to interact with A β. Electrostatic effects involved in A β40-lipid interaction are discussed.