Adsorption of amyloid beta (1-40) peptide to phosphatidylethanolamine monolayers.

Abstract

The aggregation of soluble, nontoxic amyloid beta (Abeta) peptide to beta-sheet containing fibrils is assumed to be a major step in the development of Alzheimer's disease. Interactions of Abeta with neuronal membranes could play a key role in the pathogenesis of the disease. Herein, we study the adsorption of synthetic Abeta peptide to DPPE and DMPE monolayers (dipalmitoyl- and dimyristoylphosphatidylethanolamine). Both lipids exhibit a condensed monolayer state at 20 degrees C and form a similar lattice. However, at low packing densities (at large area per molecule), the length of the acyl chains determines the phase behavior, therefore DPPE is fully condensed whereas DMPE exhibits a liquid-expanded state with a phase transition at approximately 5-6 mNm(-1). Adsorption of Abeta to DPPE and DMPE monolayers at low surface pressure leads to an increase of the surface pressure to approximately 17 mNm(-1). The same was observed during adsorption of the peptide to a pure air-water interface. Grazing incidence X-ray diffraction (GIXD) experiments show no influence of Abeta on the lipid structure. The adsorption kinetics of Abeta to a DMPE monolayer followed by IRRAS (infrared reflection absorption spectroscopy) reveals the phase transition of DMPE molecules from liquid-expanded to condensed states at the same surface pressure as for DMPE on pure water. These facts indicate no specific interactions of the peptide with either lipid. In addition, no adsorption or penetration of the peptide into the lipid monolayers was observed at surface pressures above 30 mNm(-1). IRRAS allows the measurement of the conformation and orientation of the peptide adsorbed to the air-water interface and to a lipid monolayer. In both cases, with lipids at surface pressures below 20 mNm(-1) and at the air-water interface, adsorbed Abeta has a beta-sheet conformation and these beta-sheets are oriented parallel to the interface.