摘要
The formation of biomolecular condensates mediated by a coupling of associative and segregative phase transitions plays a critical role in controlling diverse cellular functions in nature. This has inspired the use of phase transitions to design synthetic systems. While design rules of phase transitions have been established for many synthetic intrinsically disordered proteins, most efforts have focused on investigating their phase behaviors in a test tube. Here, we present a rational engineering approach to program the formation and physical properties of synthetic condensates to achieve intended cellular functions. We demonstrate this approach through targeted plasmid sequestration and transcription regulation in bacteria and modulation of a protein circuit in mammalian cells. Our approach lays the foundation for engineering designer condensates for synthetic biology applications.
摘要译文
生物分子冷凝物的形成是通过关联和分离相变的耦合介导的，在控制自然界的各种细胞功能中起着至关重要的作用。这启发了使用相变到设计合成系统的使用。尽管已经针对许多合成的固有无序蛋白质建立了相变的设计规则，但大多数努力都集中在测试管中研究其相位行为。在这里，我们提出了一种合理的工程方法，以编程合成冷凝物的形成和物理特性，以实现预期的细胞功能。我们通过细菌中靶向的质粒螯合和转录调节证明了这种方法，并调节了哺乳动物细胞中蛋白质回路的调节。我们的方法为合成生物学应用的工程设计师凝结基础奠定了基础。
Yifan DaiMina FaragLingchong You. Programmable synthetic biomolecular condensates for cellular control[J]. Nature Chemical Biology, 2023,19(4)