  Phase separation of intrinsically disordered proteins is important for the
formation of membraneless organelles, or biomolecular condensates, which play
key roles in the regulation of biochemical processes within cells. In this
work, we investigated the phase separation of different sequences of a
coarse-grained model for intrinsically disordered proteins and discovered a
surprisingly rich phase behavior. We studied both the fraction of total
hydrophobic parts and the distribution of hydrophobic parts. Not surprisingly,
sequences with larger hydrophobic fractions showed conventional liquid-liquid
phase separation. The location of the critical point was systematically
influenced by the terminal beads of the sequence, due to changes in interfacial
composition and tension. For sequences with lower hydrophobicity, we observed
not only conventional liquid-liquid phase separation, but also reentrant phase
behavior, in which the liquid phase density decreases at lower temperatures.
For some sequences, we observed formation of open phases consisting of
aggregates, rather than a normal liquid. These aggregates had overall lower
densities than the conventional liquid phases, and exhibited complex geometries
with large interconnected string-like or membrane-like clusters. Our findings
suggest that minor alterations in the ordering of residues may lead to large
changes in the phase behavior of the protein, a fact of significant potential
relevance for biology.
