Investigating the Effects of Molecular Crowding on the Kinetics of Protein Aggregation

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.