多维超高分辨率显微镜揭示了FUS凝聚物老化中的纳米级表面聚合物
Changdong He1, Chun Ying Wu1, Wan Li1
1Department of Chemistry, University of California, Berkeley California94720, United States.
Journal of the American Chemical Society
|October 2, 2023
概括
生物分子凝聚物如FUS蛋白经历与衰老相关的变化. 超分辨率显微镜揭示了在凝结体表面形成的纳米级粉体聚合物,阻碍了扩散并影响了细胞功能.
科学领域:
- 生物物理
- 细胞生物学
- 生物分子凝结物
背景情况:
- 细胞内液体-液体相分离 (LLPS) 形成细胞功能至关重要的无膜器官.
- FUS蛋白质凝聚物模拟LLPS成熟和与衰老相关的转变,但内部结构难以解决.
- 了解凝结物衰老机制和物理性质对于疾病洞察至关重要.
研究的目的:
- 在FUS蛋白质凝聚物中研究纳米级异质性和衰老演变.
- 阐明FUS冷凝剂成熟过程中的结构和物理变化.
- 应用高级超分辨率显微镜来分辨微米大小的凝结体内部.
主要方法:
- 使用多维超分辨率显微镜,包括光谱分辨率单分子局部化显微镜 (SR-SMLM) 和溶色染料.
- 采用化胺探针的SMLM来识别聚合物的类型.
- 应用单分子位移/扩散性映射 (SMdM) 来评估局部扩散动态.
主要成果:
- 在FUS凝聚物的表面发现了明显的疏水性纳米领域.
- 使用特定的探针确定这些纳米域为粉状聚合物.
- 证明这些纳米聚合物显著阻碍了凝聚物内的局部扩散.
- 在老化或剪切时观察到表面纳米聚合物的渐进扩张,形成低扩散性外.
结论:
- 揭示了单元FUS凝聚物的纳米结构安排和衰老机制.
- 展示了纳米级LLPS分析的多维超分辨率显微镜的协同作用.
- 开辟了研究纳米级LLPS系统的新途径,
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