Model for disordered proteins with strongly sequence-dependent liquid phase behavior

TL;DR

This study explores how sequence variations in disordered proteins influence their phase separation behavior, revealing diverse phenomena including reentrant phases and aggregate formation, which are crucial for understanding cellular organization.

Contribution

The paper introduces a coarse-grained model that captures the sequence-dependent phase behavior of disordered proteins, highlighting the impact of hydrophobic distribution on phase phenomena.

Findings

Sequences with higher hydrophobicity show conventional phase separation.

Terminal residues significantly affect the critical point and interfacial properties.

Low hydrophobicity sequences exhibit reentrant phase behavior and aggregate formation.

Abstract

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.