Maxwell Centre, Cavendish Laboratory, Department of Physics, University of Cambridge, J J Thomson Avenue, Cambridge, CB3 0HE, UK.
Yusuf Hamied Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK.
Sci Rep. 2021 Jul 27;11(1):15241. doi: 10.1038/s41598-021-94309-y.
Biomolecular condensates are liquid-like membraneless compartments that contribute to the spatiotemporal organization of proteins, RNA, and other biomolecules inside cells. Some membraneless compartments, such as nucleoli, are dispersed as different condensates that do not grow beyond a certain size, or do not present coalescence over time. In this work, using a minimal protein model, we show that phase separation of binary mixtures of scaffolds and low-valency clients that can act as surfactants-i.e., that significantly reduce the droplet surface tension-can yield either a single drop or multiple droplets that conserve their sizes on long timescales (herein 'multidroplet size-conserved' scenario'), depending on the scaffold to client ratio. Our simulations demonstrate that protein connectivity and condensate surface tension regulate the balance between these two scenarios. The multidroplet size-conserved scenario spontaneously arises at increasing surfactant-to-scaffold concentrations, when the interfacial penalty for creating small liquid droplets is sufficiently reduced by the surfactant proteins that are preferentially located at the interface. In contrast, low surfactant-to-scaffold concentrations enable continuous growth and fusion of droplets without restrictions. Overall, our work proposes one thermodynamic mechanism to help rationalize how size-conserved coexisting condensates can persist inside cells-shedding light on the roles of protein connectivity, binding affinity, and droplet composition in this process.
生物分子凝聚物是类似液体的无膜隔室，有助于蛋白质、RNA 和细胞内其他生物分子的时空组织。一些无膜隔室，如核仁，是作为不同的凝聚物分散的，这些凝聚物不会超过一定的大小，也不会随着时间的推移而合并。在这项工作中，我们使用一个最小的蛋白质模型表明，支架和低价客户的二元混合物的相分离可以作为表面活性剂 - 即，显著降低液滴表面张力 - 可以产生单个液滴或多个液滴，这些液滴在长时间尺度上保持其大小（本文中称为“多液滴大小守恒”情景），这取决于支架与客户的比例。我们的模拟表明，蛋白质连接和凝聚物表面张力调节这两种情况之间的平衡。当界面处的小液滴形成的界面惩罚由于优先位于界面处的表面活性剂蛋白而被充分降低时，多液滴大小守恒情景在表面活性剂与支架的浓度增加时自发出现。相比之下，低表面活性剂与支架的浓度允许液滴不受限制地连续生长和融合。总的来说，我们的工作提出了一种热力学机制，有助于合理化大小守恒的共存凝聚物如何在细胞内持续存在 - 阐明了蛋白质连接、结合亲和力和液滴组成在这个过程中的作用。
