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

J Phys Chem Lett. 2012 May 17;3(10):1258-63. doi: 10.1021/jz300459n. Epub 2012 Apr 30.

Abstract

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.

Keywords: atomic force microscopy; crystallization mechanism; friction coefficient; glucose isomerase; rate laws; scanning confocal microscopy; step kinetic coefficient.