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bioRxiv · 10.1101/2020.08.05.238584

Investigating the effects of molecular crowding on the kinetics of protein aggregation

Schreck, J. S.·Bridstrup, J.·Yuan, J.-M.
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Abstract

The thermodynamics and kinetics of protein folding and protein aggregation in vivo are of great importance in numerous scientific areas including fundamental biophysics research, nanotechnology, and medicine. However, these processes remain poorly understood in both in vivo and in vitro systems. Here we extend an established model for protein aggregation that is based on the kinetic equations for the moments of the polymer size distribution by introducing macromolecular crowding particles into the model using scaled-particle and transition-state theories. The model predicts that the presence of crowders can either speed up, cause no change to, or slow down the progress of the aggregation compared to crowder-free solutions, in striking agreement with experimental results from nine different amyloid-forming proteins that utilized dextran as the crowder. These different dynamic effects of macromolecular crowding can be understood in terms of the change of excluded volume associated with each reaction step.

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Schreck, J. S., Bridstrup, J., Yuan, J.-M.. 2020-08-06. Investigating the effects of molecular crowding on the kinetics of protein aggregation. https://doi.org/10.1101/2020.08.05.238584

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