Investigating the molecular driving forces of liquid-liquid phase separation in intrinsically disordered proteins*

It is increasingly recognized that liquid-liquid phase seperation (LLPS) serves as a fundamental mechanism employed by cells to establish transient spatiotemporal organization of the cytoplasm which is achieved through the formation of biomolecular condensates. The molecular forces driving this intricate process, predominantly involving intrinsically disordered proteins (IDPs) in the cell, remain inadequately characterised.  Hence, an enhanced understanding of these determinants could offer insight into cellular organisation, as well as shedding light on the pathogenesis of protein condensation diseases.

We have investigated these molecular drivers using a model for intrinsically disordered proteins. By experimentally mapping the LLPS phase boundary, we have shown that the binodal is sensitive to both changes in protein structure and protein-protein interactions. Hence, we shed light on the cooperative relationship between entropic and enthalpic components of the free energy which drive the phase separation of IDPs.