Qian Daoyuan, Ausserwoger Hannes, Sneideris Tomas, Farag Mina, Pappu Rohit V, Knowles Tuomas P J
Centre for Misfolding Diseases, Yusuf Hamied Department of Chemistry, University of Cambridge, CB2 1EW Cambridge, United Kingdom.
Department of Biomedical Engineering and Center for Biomolecular Condensates, Washington University in St. Louis, St. Louis, MO 63130.
Proc Natl Acad Sci U S A. 2024 Aug 13;121(33):e2407453121. doi: 10.1073/pnas.2407453121. Epub 2024 Aug 5.
Phase separation in aqueous solutions of macromolecules underlies the generation of biomolecular condensates in cells. Condensates are membraneless bodies, representing dense, macromolecule-rich phases that coexist with the dilute, macromolecule-deficient phases. In cells, condensates comprise hundreds of different macromolecular and small molecule solutes. How do different solutes contribute to the driving forces for phase separation? To answer this question, we introduce a formalism we term energy dominance analysis. This approach rests on analysis of shapes of the dilute phase boundaries, slopes of tie lines, and changes to dilute phase concentrations in response to perturbations of concentrations of different solutes. The framework is based solely on conditions for phase equilibria in systems with arbitrary numbers of macromolecules and solution components. Its practical application relies on being able to measure dilute phase concentrations of the components of interest. The dominance framework is both theoretically facile and experimentally applicable. We present the formalism that underlies dominance analysis and establish its accuracy and flexibility by deploying it to analyze phase diagrams probed in simulations and in experiments.
大分子水溶液中的相分离是细胞中生物分子凝聚物形成的基础。凝聚物是无膜体，代表与稀的、大分子缺乏相共存的致密、富含大分子的相。在细胞中，凝聚物包含数百种不同的大分子和小分子溶质。不同的溶质如何对相分离的驱动力产生影响？为了回答这个问题，我们引入了一种我们称之为能量优势分析的形式体系。这种方法基于对稀相边界形状、系线斜率以及不同溶质浓度扰动下稀相浓度变化的分析。该框架仅基于具有任意数量大分子和溶液组分的系统中的相平衡条件。其实际应用依赖于能够测量感兴趣组分的稀相浓度。优势框架在理论上易于理解且在实验中适用。我们展示了构成优势分析基础的形式体系，并通过将其应用于分析模拟和实验中探测的相图来确定其准确性和灵活性。
