Viscosity and Diffusion: Crowding and Salt Effects in Protein Solutions

TL;DR

This study combines experimental and theoretical approaches to analyze how protein and salt concentrations affect the viscosity and diffusion in bovine serum albumin solutions, revealing limitations of existing theoretical relations.

Contribution

It introduces a semi-quantitative theoretical model that accurately predicts static and dynamic properties of protein solutions, and examines the validity of the generalized Stokes-Einstein relation.

Findings

Maximum viscosity at low protein and salt concentrations due to electrostatic repulsion

Significant violation of the GSE relation in semi-dilute and low-salt conditions

Theoretical model reproduces experimental data with high accuracy

Abstract

We report on a joint experimental-theoretical study of collective diffusion in, and static shear viscosity of solutions of bovine serum albumin (BSA) proteins, focusing on the dependence on protein and salt concentration. Data obtained from dynamic light scattering and rheometric measurements are compared to theoretical calculations based on an analytically treatable spheroid model of BSA with isotropic screened Coulomb plus hard-sphere interactions. The only input to the dynamics calculations is the static structure factor obtained from a consistent theoretical fit to a concentration series of small-angle X-ray scattering (SAXS) data. This fit is based on an integral equation scheme that combines high accuracy with low computational cost. All experimentally probed dynamic and static properties are reproduced theoretically with an at least semi-quantitative accuracy. For lower protein concentration and low salinity, both theory and experiment show a maximum in the reduced viscosity, caused by the electrostatic repulsion of proteins. The validity range of a generalized Stokes-Einstein (GSE) relation connecting viscosity, collective diffusion coefficient, and osmotic compressibility, proposed by Kholodenko and Douglas [PRE 51, 1081 (1995)] is examined. Significant violation of the GSE relation is found, both in experimental data and in theoretical models, in semi-dilute systems at physiological salinity, and under low-salt conditions for arbitrary protein concentrations.