Imaging Aβ(1–42) fibril elongation reveals strongly polarised growth and growth incompetent states

Literature Information

Publication Date 2017-10-03
DOI 10.1039/C7CP03412A
Impact Factor 3.676
Authors

Laurence J. Young, Gabriele S. Kaminski Schierle, Clemens F. Kaminski


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Abstract

The major hallmark of Alzheimer's disease is the deposition of plaques of amyloid fibrils formed from amyloid-β (Aβ) peptides. Kinetic studies have contributed significantly towards a mechanistic understanding of amyloid fibril self-assembly, however dynamic features of the aggregation process cannot be captured using ensemble methods. Here we present an assay for imaging Aβ42 aggregation dynamics at the single fibril level, allowing for the quantitative extraction of concentration and temperature dependent kinetic parameters. From direct observation of elongation using TIRF and super-resolution optical microscopy, we find that Aβ42 fibril growth is strongly polarized, with fast and slow growing ends arising from different elongation rates, but also from a growth incompetent state, which dominates the process at the slow growing end. Our findings reveal the surprising complexity of the Aβ42 fibril elongation reaction at the microscopic level.

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Physical Chemistry Chemical Physics

Physical Chemistry Chemical Physics
CiteScore: 5.5
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Physical Chemistry Chemical Physics (PCCP) is an international journal co-owned by 19 physical chemistry and physics societies from around the world. This journal publishes original, cutting-edge research in physical chemistry, chemical physics and biophysical chemistry. To be suitable for publication in PCCP, articles must include significant innovation and/or insight into physical chemistry; this is the most important criterion that reviewers and Editors will judge against when evaluating submissions. The journal has a broad scope and welcomes contributions spanning experiment, theory, computation and data science. Topical coverage includes spectroscopy, dynamics, kinetics, statistical mechanics, thermodynamics, electrochemistry, catalysis, surface science, quantum mechanics, quantum computing and machine learning. Interdisciplinary research areas such as polymers and soft matter, materials, nanoscience, energy, surfaces/interfaces, and biophysical chemistry are welcomed if they demonstrate significant innovation and/or insight into physical chemistry. Joined experimental/theoretical studies are particularly appreciated when complementary and based on up-to-date approaches.

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