膨胀显微镜在核应激过程中提供了对核重组和核焦点形成的纳米尺度洞察力
Katelyn R Alley1, Katelyn M Wyatt1, Adam C Fries2
1Department of Chemistry and Biochemistry, University of Oregon, Eugene, Oregon 97403, United States.
ACS chemical biology
|May 20, 2025
概括
扩展显微镜 (ExM) 揭示了在压力期间纳米级核细胞结构的变化. 这种技术精确地描绘了细胞核和核焦点,为细胞对药物的反应提供了新的见解.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 显微镜技术 显微镜技术
背景情况:
- 细胞核是核糖体生物发生的重要无膜器官,具有对细胞信号和疾病敏感的复杂纳米组织.
- 了解细胞核的结构动态对于破译细胞反应和疾病机制至关重要.
研究的目的:
- 探索扩展显微镜 (ExM) 对核细胞和其他无膜有机体的高分辨率成像的潜力.
- 研究在诱导核应力下核核中的结构和功能变化.
- 阐明核子应激反应的早期机制及其分子基础.
主要方法:
- 应用双蛋白扩展显微镜 (双-proExM) 和点击扩展显微镜 (点击-ExM) 进行纳米级成像.
- 使用oxaliplatin,actinomycin D和基于的化合物诱导核子应激.
- 核细胞结构和功能变化的时间依赖分析.
主要成果:
- 使用ExM技术实现了前所未有的约45±2nm的核分辨率.
- 在RNA聚合酶I隔离之前的核细胞应激反应中确定了新的阶段.
- 可视化纳米级蛋白质重新排列与RNA转录相关,并确定了活跃转录的位置.
- 在长时间的压力下观察到纤维素和NPM1分离到核等离子体焦点,以纳米分辨率成像.
结论:
- 扩展显微镜 (ExM) 提供了极高的纳米级精度,用于像核细胞这样的无膜有机体的成像.
- 这项研究揭示了新的形态细节,并阐明了核细胞应激反应的早期分子机制.
- ExM是一种强大的工具,可以促进对细胞结构,功能和对细胞干扰的反应的理解.
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