Aggregation of Alzheimer amyloid beta peptide (1-42) on the multivalent sulfonated sugar interface.

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.