Wang Jiahui, Sundaravadivelu Devarajan Dinesh, Nikoubashman Arash, Mittal Jeetain
Artie McFerrin Department of Chemical Engineering, Texas A&M University, College Station, TX 77843, United States.
Institute of Physics, Johannes Gutenberg University Mainz, Staudingerweg 7, 55128 Mainz, Germany.
bioRxiv. 2023 Jul 31:2023.07.29.551102. doi: 10.1101/2023.07.29.551102.
Polymer models serve as useful tools for studying the formation and physical properties of biomolecular condensates. In recent years, the interface dividing the dense and dilute phases of condensates has been discovered to be closely related to their functionality, but the conformational preferences of the constituent proteins remain unclear. To elucidate this, we perform molecular simulations of a droplet formed by liquid‒liquid phase separation of homopolymers, as a surrogate model for the prion-like low-complexity domains. By systematically analyzing the polymer conformations at different locations in the droplet, we find that the chains become compact at the droplet interface compared to the droplet interior. Further, segmental analysis revealed that the end sections of the chains are enriched at the interface to maximize conformational entropy, and are more expanded than the middle sections of the chains. We find that the majority of chain segments lie tangential to the droplet surface and only the chain ends tend to align perpendicular to the interface. These trends also hold for the natural proteins FUC LC and LAF-1 RGG, which exhibit more compact chain conformations at the interface compared with the droplet interior. Our findings provide important insights into the interfacial properties of biomolecular condensates and highlight the value of using simple polymer physics models to understand the underlying mechanisms.
聚合物模型是研究生物分子凝聚物的形成和物理性质的有用工具。近年来，人们发现凝聚物的浓相和稀相之间的界面与其功能密切相关，但组成蛋白质的构象偏好仍不清楚。为了阐明这一点，我们对由均聚物的液-液相分离形成的液滴进行了分子模拟，作为朊病毒样低复杂性结构域的替代模型。通过系统地分析液滴中不同位置的聚合物构象，我们发现与液滴内部相比，链在液滴界面处变得紧凑。此外，片段分析表明，链的末端部分在界面处富集，以最大化构象熵，并且比链的中间部分更伸展。我们发现，大多数链段与液滴表面相切，只有链端倾向于垂直于界面排列。这些趋势也适用于天然蛋白质FUC LC和LAF-1 RGG，与液滴内部相比，它们在界面处表现出更紧凑的链构象。我们的研究结果为生物分子凝聚物的界面性质提供了重要见解，并突出了使用简单聚合物物理模型来理解潜在机制的价值。
