Heterogeneous structure (and order) of disordered FUS condensation

Formation of membraneless liquid-like biomolecular condensates (BCs) via liquid-liquid phase separation of disordered proteins is responsible for many behaviors in cells, specifically stress granule formation, chromatin organization, and RNA transcription. Structural changes of these BCs can be triggered by external stimuli such as pH, salt, or temperature as well as surface interactions. Often external stimuli can facilitate aberrant phase transitions or non-native multivalent interactions of these disordered proteins, which eventually leads to solidification. Here, I describe our studies of the structural and biophysical properties of FUS condensation after thermal shock, at hydrophobic interfaces, and at lipid interfaces using a combination of cutting-edge molecular microscopy and spectroscopy to reveal the diverse molecular states that FUS inhabits. In contrast to the disordered state observed in conventional liquid BCs, FUS under these different conditions forms condensates with heterogeneous structure and surprising ordering. Moreover, we find that interfaces can catalyze FUS assembly at concentrations less than 50-fold required in bulk.