Nonfibrous β-structured aggregation of an Aβ model peptide (Ad-2α) on GM1/DPPC mixed monolayer surfaces

Adsorption and aggregation of transformed peptides and proteins onto the cell membrane surface is commonly associated with forms of amyloidosis such as Alzheimer's disease and prion disease. To address dynamic features of these pathological phenomena molecularly, the in situ Ad-2α model peptide deposition on glycolipid-containing monolayers was studied by using a 9 MHz quartz-crystal microbalance (QCM). The Ad-2α peptide has two amphiphilic α-helix segments, each modified with a 1-adamantanecarbonyl group at the N-terminal as a hydrophobic defect. The peptide folds in a 2α-helix structure in the bulk solution. In the presence of mixed monolayers of glycolipids (GM1, asialo-GM1, GM3, or LacCer) and/or dipalmitoyl phosphatidylcholine (DPPC) laminated on the QCM plate, the peptide deposition and the conformational change to β-structure on the monolayers were accelerated. The adsorption kinetics and the amount of Ad-2α were dependent on the sort and contents of the glycolipid in the DPPC matrix. Although the Ad-2α peptide adsorbs onto most of the glycolipid membranes as monolayer coverage, it adsorbed largely onto the GM1/DPPC (30/70 mol%) mixed monolayer with characteristic kinetic behaviors. The accumulation of β-structured nonfibrous aggregations was confirmed by AFM and fluorescence microscopy with Thioflavin T (ThT).

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