On the role of surface tension in the stabilization of globular proteins

Abstract

The stabilization of proteins by a variety of co-solvents can be related to their property of increasing the surface tension of water. It is demonstrated that, during the thermal unfolding of proteins, this increase of the surface tension can be overcome by the increase in the temperature of the solution at the midpoint of the transition, T,, and the weak binding of co-solvent molecules. Three such co-solvents were studied: trehalose, lysine hydrochloride (LysHCl), and arginine hydrochloride (ArgHC1). Trehalose and LysHCl increase the midpoint of T,. The increase of the surface tension by addition of trehalose is completely compensated by its decrease due to the increase in T,. However, for LysHC1, the increase of the surface tension by the co-solvent is partly reduced by its binding to the protein. Later studies on the preferential interaction2 of proteins with a variety of co-solvents have identified the surface tension ef-'The term preferential interaction refers to the net interaction between the protein and the solvent components, water and the co-solvent, as measured by an equilibrium thermodynamic approach, such as dialysis equilibrium. When the interactions are weak, as is the case with co-solvents, such as sugars, glycerol, amino acids, or urea, the measured quantity is the net balance between the weak interactions (binding) of water and co-solvent molecules to the protein over its entire surface. If, on average, the affinity of protein surface loci for the co-solvent is greater than that for water, the dialysis equilibrium experiment will result in an excess of co-solvent at the protein surface over its concentration in the bulk solvent, and the measured binding stoichiometry will be positive, which means that co-solvent is preferentially bound relative to water. In that case, the "preferential binding" will be positive. In the converse case, in which, on average, the affinity of the protein surface loci is greater for water than for co-solvent molecules, there will be an excess of water at the protein surface over its concentration in the 372

Thermal and Solution Stability of Lysozyme in the Presence of Sucrose, Glucose, and Trehalose

“…13,30 The preferential hydration mechanism proposes that sugars are excluded from the environment around the protein and are replaced by water. 13,30,41 The preferential exclusion mechanism is supported by the increase in surface tension of water surrounding the protein due to the addition of sugars. 13,30,41 However, the exact reason for the enhanced structural stabilization of proteins in the presence of sugars is still unclear.…”

A thermodynamic analysis of the binding interaction between polysorbate 20 and 80 with human serum albumins and immunoglobulins: A contribution to understand colloidal protein stabilisation

“…Timasheff and coworkers [31,32] have developed a theory explaining the protein stabilisation effect, induced by the presence of detergents, being related to a preferential exclusion mechanism. Another theory considers the amphiphile nature of detergents.…”

Promotion and Suppression of Thermal Aggregation of β-Lactoglobulin by Arginine: A Concentration Dependent Mechanism

“…The stability of the native state of dissolved proteins is generally not affected by the presence of L-arginine. Earlier it was reported that L-arginine has been found to destabilize RNaseA [13] and Cytochrome C [14] slightly. On the other hand, Reddy et al (2005) hardly found any destabilizing effect of L-arginine.HCl up to concentrations level of 1.0 M in the case of hen egg white Lysozyme [15].…”