Lin Andrew Z, Ruff Kiersten M, Jalihal Ameya, Dar Furqan, King Matthew R, Lalmansingh Jared M, Posey Ammon E, Seim Ian, Gladfelter Amy S, Pappu Rohit V
Division of Biology and Biomedical Sciences, Plant and Microbial Biosciences, Washington University in St. Louis, St. Louis, MO 63130, USA.
Department of Biomedical Engineering and Center for Biomolecular Condensates, James F. McKelvey School of Engineering, Washington University in St. Louis, St. Louis, MO 63130, USA.
Res Sq. 2023 Feb 8:rs.3.rs-2440278. doi: 10.21203/rs.3.rs-2440278/v1.
Macromolecular phase separation underlies the regulated formation and dissolution of biomolecular condensates. What is unclear is how condensates of distinct and shared macromolecular compositions form and coexist within cellular milieus. Here, we use theory and computation to establish thermodynamic criteria that must be satisfied to achieve compositionally distinct condensates. We applied these criteria to an archetypal ribonucleoprotein condensate and discovered that demixing into distinct protein-RNA condensates cannot be the result of purely thermodynamic considerations. Instead, demixed, compositionally distinct condensates arise due to asynchronies in timescales that emerge from differences in long-lived protein-RNA and RNA-RNA crosslinks. This type of dynamical control is also found to be active in live cells whereby asynchronous production of molecules is required for realizing demixed protein-RNA condensates. We find that interactions that exert dynamical control provide a versatile and generalizable way to influence the compositions of coexisting condensates in live cells.
大分子相分离是生物分子凝聚物形成和解聚的基础。目前尚不清楚的是，具有不同和共享大分子组成的凝聚物如何在细胞环境中形成并共存。在这里，我们运用理论和计算方法来建立实现组成不同的凝聚物必须满足的热力学标准。我们将这些标准应用于一个典型的核糖核蛋白凝聚物，发现分离成不同的蛋白质-RNA凝聚物并非纯粹热力学因素所致。相反，分离出的、组成不同的凝聚物是由于长寿命蛋白质-RNA和RNA-RNA交联差异导致的时间尺度异步性而产生的。这种动力学控制在活细胞中也很活跃，即实现分离的蛋白质-RNA凝聚物需要分子的异步产生。我们发现，施加动力学控制的相互作用为影响活细胞中共存凝聚物的组成提供了一种通用且可推广的方式。
