远红色的化学基因激酶生物传感器可以实现信号网络的多重和超分辨率成像
Michelle S Frei1,2, Samantha A Sanchez3,4, Xinchang He3,5
1Department of Pharmacology, University of California, San Diego, La Jolla, CA, USA. michelle.frei@org.chem.ethz.ch.
Nature biotechnology
|April 21, 2025
概括
新的化学遗传生物传感器提供高分辨率的四维图像,细胞信号网络. 这一突破允许对激酶活性进行详细的研究,并在活细胞中检测多重分析物.
科学领域:
- 生物医学研究生物医学研究
- 细胞生物学 细胞生物学
- 分子成像学分子成像学
背景情况:
- 光生物传感器可以通过活细胞测量细胞信号.
- 当前的生物传感器缺乏空间时空网络分析的分辨率和维度.
- 调查复杂的信号网络需要先进的成像技术.
研究的目的:
- 开发高度敏感的化学基因激酶活性生物传感器.
- 为了实现四维 (4D) 活动成像和超高分辨率显微镜.
- 增加生物传感器多重复合的维度,以便同时检测分析物.
主要方法:
- 使用HaloTag7自标签标签与远红发射合成光体.
- 采用刺激辐射消耗 (STED) 和其他高分辨率显微镜技术.
- 在单个活细胞中开发多重成像,用于多达五种分析物.
主要成果:
- 实现了高分辨率的四维成像,对激酶活性进行四维成像.
- 通过使用STED成像,研究了单个氨酸涂层坑中的蛋白质激酶A活性.
- 在GPCR激活的下游进行了量化,时空网络状态测量.
结论:
- 这种新的化学遗传生物传感器技术克服了分辨率和维度限制.
- 能够在多个尺度上对信号网络进行详细的查询.
- 为生物医学研究和药物发现提供先进的活细胞成像.
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