Statistical thermodynamics of casein aggregation: Effects of salts and water

Salts, when added to milk, profoundly influence casein aggregation. Even though this well-known phenomenon has been widely exploited, there are still many unanswered questions. How do salts affect casein aggregation? Does water contribute significantly to the aggregation change? The key to answering these questions comes from statistical thermodynamics, i.e. the principles of physics that can link macroscopic data to the collective behaviour of molecules. We present two theoretical approaches. A rigorous approach which demands far more measurements than reported hitherto; and an approximate, pragmatic approach. It bases on stoichiometric models (isodesmic model for aggregation equilibria and von Smoluchowski model for kinetics) that can yield information on protein-water and protein-salt interactions from 'real-life' experimental measurements on model systems available in a variety of formats. Using experimental data from the literature, casein aggregation, in the absence of κ-casein, has been shown to be modulated by protein-salt interaction, while the contribution from water structure changes has been shown to be negligible.