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Aggregation of Alzheimer Amyloid β Peptide (1−42) on the Multivalent Sulfonated Sugar Interface

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journal contribution
posted on 2010-06-16, 00:00 authored by Tomohiro Fukuda, Erino Matsumoto, Shunsuke Onogi, Yoshiko Miura
The mechanism of amyloidosis of amyloid β (1−42) (Aβ (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 Aβ (1−42) aggregates on the substrates were investigated by dynamic-mode AFM and FTIR-RAS. Aβ (1−42) interactions with multivalent sugars were evaluated by surface plasmon resonance, and the cytotoxicity of Aβ (1−42) to HeLa cells was evaluated by MTT assay. Morphological images showed, interestingly, that Aβ (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 Aβ (1−42) was related to the change of binding mode, and the binding mode was dependent on the multivalency of the sugar. Globular Aβ (1−42) was more toxic than fibrillar Aβ (1−42) to HeLa cells. These results suggested that the multivalency of sugars for the amyloidosis of Aβ (1−42) was significant in its morphology and aggregation effects at the surface of the cell membrane mimic.

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