Preferential Intercalation of Human Amyloid-β Peptide into Interbilayer Region of Lipid-Raft Membrane in Macromolecular Crowding Environment.

This study focuses on the interaction of human amyloid β-peptide (Aβ) with a lipid-raft model membrane under macromolecular crowding conditions that mimic the intracellular environment. Aβ is central to the development of Alzheimer's disease (AD) and has been studied extensively to determine the molecular mechanisms of Aβ-induced cellular dysfunctions underlying the pathogenesis of AD. According to evidence from spectroscopic studies, ganglioside clusters are key to the fibrillization process of Aβ. Gangliosides are a major component of glycosphingolipids and are acidic lipids of the central nervous system known to form so-called lipid rafts. In this study, the small unilamellar vesicle (SUV) membrane, composed of monosialogangliosides, cholesterol, and 1,2-dipalmitoyl- sn-glycero-3-phosphocholine, did not show any structural changes after the addition of Aβ under noncrowding conditions. However, the addition of Aβ under crowding conditions induced shape deformation and aggregation to SUV resulting in multilamellar stacking. The time evolution of the lamellar peak suggested the preferential cohesion or intercalation of the Aβ peptide into the interbilayer region. This phenomenon was only observed at the gel (Lβ) phase. These results suggest that an intracellular crowding environment promotes Aβ-membrane interaction and a selective accumulation of Aβ peptides into the interbilayer regions.