Department of Chemical and Biological Engineering, Princeton University, Princeton, New Jersey 08544, USA.
Department of Physics, Princeton University, Princeton, New Jersey 08544, USA.
J Chem Phys. 2020 Feb 21;152(7):075101. doi: 10.1063/1.5141095.
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 re-entrant phase behavior in which the liquid phase density decreases at lower temperatures. For some sequences, we observed the 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.
无定形蛋白质的相分离对于形成无膜细胞器或生物分子凝聚体很重要，这些凝聚体在细胞内生化过程的调节中起着关键作用。在这项工作中，我们研究了无定形蛋白质粗粒模型的不同序列的相分离，并发现了出乎意料的丰富相行为。我们研究了总疏水区分数和疏水区分布。毫不奇怪，疏水区分数较大的序列表现出常规的液-液相分离。由于界面组成和张力的变化，序列末端珠的位置系统地影响临界点的位置。对于疏水性较低的序列，我们不仅观察到常规的液-液相分离，还观察到再进入相行为，其中液相密度在较低温度下降低。对于某些序列，我们观察到由聚集体组成的开放相的形成，而不是正常的液体。这些聚集体的密度总体上低于常规液体相，并表现出复杂的几何形状，具有大的互连串状或膜状簇。我们的发现表明，残基排列的微小改变可能导致蛋白质相行为的巨大变化，这一事实对生物学具有重要的潜在意义。
