Alzheimer's amyloid-beta intermediates generated using polymer-nanodiscs

Bikash R. Sahoo; Takuya Genjo; Michael Bekier; Sarah J. Cox; Andrea K. Stoddard; Magdalena Ivanova; Kazuma Yasuhara; Carol A. Fierke; Yanzhuang Wang; Ayyalusamy Ramamoorthy

doi:10.1039/C8CC07921H

Alzheimer's amyloid-beta intermediates generated using polymer-nanodiscs†

Bikash R. Sahoo,^a Takuya Genjo,^a Michael Bekier, II,^b Sarah J. Cox,^a Andrea K. Stoddard,^a Magdalena Ivanova,^a Kazuma Yasuhara,^c Carol A. Fierke,^ad Yanzhuang Wang^b and Ayyalusamy Ramamoorthy

*^a

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* Corresponding authors

^a Biophysics and Department of Chemistry, University of Michigan, Ann Arbor, MI 48109-1055, USA
E-mail: ramamoor@umich.edu

^b Department of Neurology, Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109-1055, USA

^c Graduate School of Materials Science, Nara Institute of Science and Technology, Ikoma, Nara 6300192, Japan

^d Texas A&M University, College Station, TX 77843, USA

Abstract

Polymethacrylate-copolymer (PMA) encased lipid-nanodiscs (∼10 nm) and macro-nanodiscs (>15 nm) are used to study Aβ_1–40 aggregation. We demonstrate that PMA-nanodiscs form a ternary association with Aβ and regulate its aggregation kinetics by trapping intermediates. Results demonstrating the reduced neurotoxicity of nanodisc-bound Aβ oligomers are also reported.

Chemical Communications

Alzheimer's amyloid-beta intermediates generated using polymer-nanodiscs†

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Alzheimer's amyloid-beta intermediates generated using polymer-nanodiscs

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