This study focuses on the interaction of human amyloid beta-peptide (A beta) with a lipid-raft model membrane under macromolecular crowding conditions that mimic the intracellular environment. A beta is central to the development of Alzheimer's disease (AD) and has been studied extensively to determine the molecular mechanisms of A beta-induced cellular dysfunctions underlying the pathogenesis of AD. According to evidence from spectroscopic studies, ganglioside clusters are key to the fibrillization process of A beta. 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 A beta under noncrowding conditions. However, the addition of A beta 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 A beta peptide into the interbilayer region. This phenomenon was only observed at the gel (L-beta) phase. These results suggest that an intracellular crowding environment promotes A beta-membrane interaction and a selective accumulation of A beta peptides into the interbilayer regions.