Exploring the Physics of Polymer-Assisted Condensation: A Polymer Physics Concept for Biomolecular Condensates

生物分子凝聚体是由蛋白质与RNA或DNA等大分子生物聚合物相互作用的局部相分离形成的。了解它们的形成和性质本质上与复杂溶剂混合物中聚合物的物理联系在一起。申请人已经开发了生物分子缩合物的通用模型，其中溶剂混合物(生物系统中的蛋白质-水混合物)的相分离是由于与聚合物(生物系统中的DNA或RNA)的弱选择性相互作用引起的。这种“聚合物辅助缩合”可以通过分子动力学模拟来证明。该模型可以用一种特殊的方式解释染色质凝聚体(异染色质)的基本性质。在这个项目中，我们想要从数学分析和计算机模拟两个方面来研究这类聚合物凝聚物的物理性质。这里的重点是外力对凝析油的影响，它在表面上的吸附，聚结效应，以及将该模型推广到含有两个以上溶剂组分的体系。我们项目的结果对生物物理学和经典聚合物物理都很有意义。溶剂混合物可以使聚合物材料中的转换过程成为可能，例如刷子和网络，就像众所周知的“共同无偿付能力”效应。理论建模将基于已建立的混合物自由能模型，分子动力学模拟主要使用聚合物和溶剂组分的粗化模型。

Biomolecular condensates are formed by local phase separation of proteins interacting with large biopolymers such as RNA or DNA. Understanding their formation and properties is intrinsically linked to the physics of polymers in complex solvent mixtures. The applicants have developed a generic model for biomolecular condensates in which phase separation of a solvent mixture (protein-water mixture in biological systems) is caused by a weak selective interaction with the polymer (DNA or RNA in biological systems). This "polymer-assisted condensation" could be demonstrated by molecular dynamics simulations. The model can explain in a particular way fundamental properties of chromatin condensates (heterochromatin). In this project we want to investigate several aspects of the physics of this class of polymer condensates both mathematically-analytically and in computer simulations. The focus here is on the influence of external forces on the condensate, its adsorption on surfaces, coalescence effects, and the generalization of the model to systems with more than two solvent components. The results of our project are of interest to both biophysics and classical polymer physics. Solvent mixtures can enable switching processes in polymer materials such as brushes and networks, as in the well known "co-nonsolvency" effect. Theoretical modeling will be based on well-established free-energy models of the mixtures, and molecular dynamics simulations mainly using coarsened models for polymers and solvent components.