Liquid-liquid phase separation is often not directly evident in solutions of globular proteins, nevertheless it is a metastable phenomenon underlying other forms of protein condensation, such as aggregation, gelation and crystallization. Of all the protein condensations, liquid-liquid phase separation is the least sensitive to the detailed features of the inter-protein attraction and therefore is most amenable to quantitative phenomenological analysis. On the basis of our experimental and theoretical investigations of liquid-liquid phase separation in solutions of gamma-crystallins and immunoglobulins we will discuss: (i) the factors which determine the location of the critical point and the shape of the coexistence curve;  (ii) use of the phase diagram as a tool for evaluating the effect of solution conditions and the presence of other solutes on the net interprotein attraction, and the consequent stability of protein solutions; (iii) examples of human diseases (cataract, cryoglobulemia) associated with liquid-liquid phase separation and protein condensation.

Protein condensation, liquid–liquid phase separation, and human disease

243rd National Meeting (2012)

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