An alternative approach to the osmotic second virial coefficient of protein solutions and its application to liquid liquid phase separation

TL;DR

This paper introduces a new thermodynamic-based method to estimate the osmotic second virial coefficient B2 from supersaturation data, aligning well with SAXS measurements near phase separation for globular proteins.

Contribution

It establishes a novel connection between B2 from SAXS and supersaturation measurements, aiding in phase behavior analysis of protein solutions.

Findings

B2 values from the new method agree with SAXS near phase separation.

The method effectively estimates B2 for globular proteins near the binodal region.

Useful for studying protein interactions and phase behavior.

Abstract

The osmotic second virial coefficient B2 is an important parameter to describe the interactions and phase behavior of protein solutions, including colloidal systems and macromolecular solutions. Another key parameter to describe the driving force of the nucleation of a new phase is the supersaturation, which is used in the classical nucleation theory framework and is connected with the favorable contribution in the Gibbs free energy in the bulk solution. In this article, we establish a connection between B2 calculated from small angle Xray scattering (SAXS) data and the values of B2 obtained from supersaturation measurements using thermodynamics considerations. The values of the second virial coefficient calculated employing this method agree with those determined via SAXS in the region near the liquid liquid phase separation border for human serum albumin and bovine serum albumin. The general relations adopted are shown to be useful for the estimation of the second virial coefficient B2 for globular proteins, in the proximity of the binodal biphasic coexistent region.