Phase separation has long been observed within aqueous mixtures of two or more different compounds, such as proteins, salts, polysaccharides and synthetic polymers. A growing body of experimental evidence indicates that phase separation also takes place inside living cells, where intrinsically disordered proteins and other molecules such as RNA are thought to assemble into membraneless organelles. These structures represent a new paradigm of intracellular organization and compartmentalization, in which biochemical processes can be coordinated in space and time. Two thermodynamic driving forces have been proposed for phase separation: the strengths of macromolecule–macromolecule and macromolecule–H₂O interactions, and the perturbation of H₂O structure about different macromolecules. In this Perspective, we propose that both driving forces act in a concerted manner to promote phase separation, which we describe in the context of the well-known structural dynamics of intrinsically disordered proteins in the cellular milieu. We further suggest that this effect can be extended to explain how the partial unfolding of globular proteins can lead to intracellular phase separation.

长期以来，人们一直在两种或更多种不同化合物（例如蛋白质，盐，多糖和合成聚合物）的水性混合物中观察到相分离。越来越多的实验证据表明，相分离也发生在活细胞内部，在活细胞中，固有紊乱的蛋白质和其他分子（例如RNA）被认为组装成无膜细胞器。这些结构代表了细胞内组织和区室化的新范式，其中生化过程可以在空间和时间上进行协调。两个热力学驱动力已经被提出了相分离：高分子系高分子及的优势大分子-H ₂ Ø互动，和H的扰动₂关于不同大分子的O结构。在这个观点中，我们提出两种驱动力以协同的方式促进相分离，这是我们在细胞环境中固有的无序蛋白的众所周知的结构动力学的背景下描述的。我们进一步建议可以扩展这种效果，以解释球状蛋白的部分展开如何导致细胞内相分离。