Li Cheng, Bian Yunqiang, Tang Yiting, Meng Lingyu, Yin Peipei, Hong Ye, Cheng Jun, Li Yuchen, Lin Jie, Tang Chao, Chen Chunlai, Li Wenfei, Qi Zhi
Center for Quantitative Biology, Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China.
Wenzhou Key Laboratory of Biophysics, Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang 325000, China.
Structure. 2025 Jan 2;33(1):62-77.e8. doi: 10.1016/j.str.2024.10.026. Epub 2024 Nov 13.
Nucleic acid and protein co-condensates exhibit diverse morphologies crucial for fundamental cellular processes. Despite many previous studies that advanced our understanding of this topic, several interesting biophysical questions regarding the underlying molecular mechanisms remain. We investigated DNA and human transcription factor p53 co-condensates-a scenario where neither dsDNA nor the protein demonstrates phase-separation behavior individually. Through a combination of experimental assays and theoretical approaches, we elucidated: (1) the phase diagram of DNA-protein co-condensates at a certain observation time, identifying a phase transition between viscoelastic fluid and viscoelastic solid states, and a morphology transition from droplet-like to "pearl chain"-like co-condensates; (2) the growth dynamics of co-condensates. Droplet-like and "pearl chain"-like co-condensates share a common initial critical microscopic cluster size at the nanometer scale during the early stage of phase separation. These findings provide important insights into the biophysical mechanisms underlying multi-component phase separation within cellular environments.
核酸和蛋白质共凝聚物呈现出对基本细胞过程至关重要的多种形态。尽管此前有许多研究增进了我们对该主题的理解，但关于潜在分子机制仍存在一些有趣的生物物理问题。我们研究了DNA与人类转录因子p53的共凝聚物——在这种情况下，双链DNA和蛋白质单独都不表现出相分离行为。通过结合实验分析和理论方法，我们阐明了：（1）在特定观察时间下DNA - 蛋白质共凝聚物的相图，确定了粘弹性流体和粘弹性固态之间的相变，以及从液滴状到“珍珠链”状共凝聚物的形态转变；（2）共凝聚物的生长动力学。在相分离早期，液滴状和“珍珠链”状共凝聚物在纳米尺度上共享一个共同的初始临界微观簇尺寸。这些发现为细胞环境中多组分相分离的生物物理机制提供了重要见解。
