Nanoscale Diffusion Regimes of Amyloid-β Studied by Liquid-Phase TEM

Abstract

This project studies the diffusion regimes of misfolded proteins amyloid-β-42 (Aβ-42) aggregates observed by liquid-TEM. Videos acquired using this technique were analysed to reconstruct particle trajectories and thus quantify their dynamic behaviour at the nanometric scale. Due to the low contrast of these protein samples, the videos were preprocessed by normalisation, clipping, Gaussian filtering, and averaging of consecutive frames. Then, regions of interest were selected, and particle tracking was performed to obtain their trajectories. From these trajectories, the mean squared displacement (MSD) was calculated and fitted using a power law to determine the diffusion exponent α. Large aggregates of diameters circa 100nm yielded α ∼ 0 and therefore they showed negligible translational mobility while for small oligomers of diameter circa 8nm the exponent α ∼ 1 showing a behaviour compatible with normal Brownian diffusion.