Observation of LLPS in Protein and Peptide solutions: Serendipitous or Ubiquitous?

Liquid-liquid phase separation (LLPS) is a well-known phenomenon in the field of colloid physics. In the past few decades, LLPS has been reported for various protein solutions. Remarkably, LLPS of protein solutions was observed in living organisms, from “cold cataract” in the eye lenses of fish to the recently reported intracellular segregation of signal protein complexes.
One interesting question is whether LLPS is a ubiquitous phenomenon for proteins or just a serendipitous observation in isolated cases? Theoretically, metastable LLPS can be expected for the particles with short-range interactions. However, LLPS of protein solutions is rarely observed, largely due to freezing of solutions and competition from crystallization and aggregation. In this talk, I will show that LLPS can be induced for many proteins and peptides using a simple experimental method. With the ability to experimentally control LLPS, we were able to explore the phase behavior of various protein systems from large monoclonal antibodies to small lipopeptides. In our studies on the non-spherical proteins, we noticed that the shape of protein molecules has some interesting effects on the phase diagram. Our studies suggest that LLPS in protein solutions is a common phenomenon, and thereby may play important roles in living organisms as well as in practical applications of proteins.