title: Aggregation of Alzheimer amyloid beta peptide (1-42) on the multivalent sulfonated sugar interface.
abstract: The mechanism of amyloidosis of amyloid beta (1-42) (Abeta (1-42)) was investigated by the well-defined glycocluster interface. We prepared monovalent, divalent, and trivalent 6-sulfo-N-acetyl-d-glucosamine (6S-GlcNAc) immobilized substrates. The morphology and secondary structure of Abeta (1-42) aggregates on the substrates were investigated by dynamic-mode AFM and FTIR-RAS. Abeta (1-42) interactions with multivalent sugars were evaluated by surface plasmon resonance, and the cytotoxicity of Abeta (1-42) to HeLa cells was evaluated by MTT assay. Morphological images showed, interestingly, that Abeta (1-42) aggregates had a tendency to form globules rather than fibrils as the valency of 6S-GlcNAc on the substrate was increased. The SPR measurements indicated that this morphological change of Abeta (1-42) was related to the change of binding mode, and the binding mode was dependent on the multivalency of the sugar. Globular Abeta (1-42) was more toxic than fibrillar Abeta (1-42) to HeLa cells. These results suggested that the multivalency of sugars for the amyloidosis of Abeta (1-42) was significant in its morphology and aggregation effects at the surface of the cell membrane mimic.
authors.affiliation: Japan Advanced Institute of Science and Technology, Nomi, Ishikawa, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Fukuda
authors.forename: Erino
authors.initials: E
authors.lastname: Matsumoto
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Onogi
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Miura
mesh_terms: D000117:Acetylglucosamine / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism*; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D000686:Amyloidosis / Q000378:metabolism* / Q000473:pathology; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D006367:HeLa Cells; D006801:Humans; D018625:Microscopy, Atomic Force; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D017510:Protein Folding; D017550:Spectroscopy, Fourier Transform Infrared; D013451:Sulfonic Acids / Q000737:chemistry / Q000378:metabolism*; D020349:Surface Plasmon Resonance
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D013451:Sulfonic Acids; C075222:amyloid beta-protein (1-42); D000117:Acetylglucosamine