Does Solution Viscosity Scale the Rate of Aggregation of Folded Proteins?

Viscosity effects on the kinetics of complex solution processes have proven hard to
predict. To test the viscosity effects on protein aggregation, we use the crystallization of the protein
glucose isomerase (gluci) as a model and employ scanning confocal and atomic force microscopies at
molecular resolution, dynamic and static light scattering, and rheometry. We add glycerol to vary
solvent viscosity and demonstrate that glycerol effects on the activation barrier for attachment of
molecules to the crystal growth sites are minimal. We separate the effects of glycerol on
crystallization thermodynamics from those on the rate constant for molecular attachment. We
establish that the rate constant is proportional to the reciprocal viscosity and to the protein
diffusivity. This finding refutes the prevailing crystal growth paradigm and illustrates the application
of fundamental kinetics laws to solution crystallization.