The contrasting roles of co-solvents in protein formulations and food products.

Protein aggregation is a major hurdle in developing biopharmaceuticals, in particular protein formulation area, but plays a pivotal role in food products. Co-solvents are used to suppress protein aggregation in pharmaceutical proteins. On the contrary, aggregation is encouraged in the process of food product making. Thus, it is expected that co-solvents play a contrasting role in biopharmaceutical formulation and food products. Here, we show several examples that utilize co-solvents, e.g., salting-out salts, sugars, polyols and divalent cations in promoting protein-protein interactions. The mechanisms of co-solvent effects on protein aggregation and solubility have been studied on aqueous protein solution and applied to develop pharmaceutical formulation based on the acquired scientific knowledge. On the contrary, co-solvents have been used in food industries based on empirical basis. Here, we will review the mechanisms of co-solvent effects on protein-protein interactions that can be applied to both pharmaceutical and food industries and hope to convey knowledge acquired through research on co-solvent interactions in aqueous protein solution and formulation to those involved in food science and provide those involved in protein solution research with the observations on aggregation behavior of food proteins.

Reentrant condensation of a multicomponent cola/milk system induced by polyphosphate.

Reentrant condensation (RC) is a protein behavior in which the protein solution shifts between the one- and two-phase state more than twice by increasing a single parameter. Although RC would be a candidate mechanism for the physicochemical design of food additives, no realistic model has been established under diverse contaminants like food materials. Here, we found that a mixture of cola and milk yielded RC. At pH 3.2-3.6, cola induced milk condensation at 30-40%, while lower or higher concentrations of cola did not. Furthermore, we reduced this cola/milk system to two pure components, casein in milk and polyphosphate (polyP) in cola, and investigated the characteristics of casein concentration and zeta potential. This was the first experimental demonstration of RC occurrence in a multicomponent system. The well-characterized cola/milk system would explore both the universal nature of proteins and the industrial application of RC.