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

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