Protein interactions and association: an open challenge for colloid science

The solution behaviour of globular proteins still presents many puzzling aspects, calling for a deeper understanding of the physical properties of lyophilic colloids. For instance, protein interactions in ‘salting-out’ conditions require to take explicitly into account ‘Donnan’ effects on the small ion distribution, while understanding of temperature and salt–specificity effects on protein solubility presumably calls for a careful analysis of hydrophobic contributions. Yet, very unexpected effects can be found even at low salt concentration. In particular, we discuss the very distinctive properties of β-lactoglobulin A (BLGA) solutions, where strong attractive interactions show up, displaying a marked non-monotonic trend as a function of the solution ionic strength. These ‘anomalous’ attractions drive very peculiar reversible association processes, resulting in the spontaneous formation of short-lived clusters with a well-defined small aggregation number. We suggest that other protein association processes of physiological interest may parallel BLGA clustering.