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Nanoscale Dynamics of Amyloid ?-42 Oligomers As Revealed by High-Speed Atomic Force Microscopy.


ABSTRACT: Amyloid ?-protein (A?) oligomers are emerging as potent neurotoxic species in Alzheimer's disease pathogenesis. Detailed characterization of oligomer structure and dynamics is necessary to develop oligomer-specific therapeutic agents. However, oligomers exist transiently, which complicates their structural analysis. One approach to mitigate these problems has been photochemical cross-linking of native oligomers. In these states, the oligomers can be isolated and purified for physical and chemical studies. Here we characterized the structure of isolated cross-linked A?42 trimers, pentamers, and heptamers with atomic force microscopy (AFM) imaging and probed their dynamics in solution using time-lapse high-speed AFM. This technique enables visualization of the structural dynamics of the oligomers at nanometer resolution on a millisecond time scale. Results demonstrate that cross-linked pentamers and heptamers are very dynamic fluctuating between a compact single-globular and multiglobular assemblies. Trimers remain in their single-globular geometry that elongates adopting an ellipsoidal shape. Biological significance of oligomers dynamics is discussed.

SUBMITTER: Banerjee S 

PROVIDER: S-EPMC5752618 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Nanoscale Dynamics of Amyloid β-42 Oligomers As Revealed by High-Speed Atomic Force Microscopy.

Banerjee Siddhartha S   Sun Zhiqiang Z   Hayden Eric Y EY   Teplow David B DB   Lyubchenko Yuri L YL  

ACS nano 20171129 12


Amyloid β-protein (Aβ) oligomers are emerging as potent neurotoxic species in Alzheimer's disease pathogenesis. Detailed characterization of oligomer structure and dynamics is necessary to develop oligomer-specific therapeutic agents. However, oligomers exist transiently, which complicates their structural analysis. One approach to mitigate these problems has been photochemical cross-linking of native oligomers. In these states, the oligomers can be isolated and purified for physical and chemica  ...[more]

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