
1.State Key Laboratory for Mesoscopic Physics and Frontiers Science Center for Nano-optoelectronics, School of Physics, Peking University, Beijing 100871, China
2.Collaborative Innovation Center of Extreme Optics, Shanxi University, Taiyuan, Shanxi 030006, China
3.State Key Laboratory of Membrane Biology, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking University, Beijing 100871, China
4.School of Mathematical Sciences, Peking University, Beijing 100871, China
5.School of Software and Microelectronics, Peking University, Beijing 100871, China
6.State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China
7.University of Chinese Academy of Sciences, Beijing 100049, China
8.National Laboratory of Biomacromolecules, Chinese Academy of Sciences Center for Excellence in Biomacromolecules, Institute of Biophysics, Beijing 100101, China
9.Institute for Brain Research and Rehabilitation (IBRR), Guangdong Key Laboratory of Mental Health and Cognitive Science, South China Normal University, Guangzhou, China
10.Collaborative Innovation Center of Quantum Matter, Peking University, Beijing 100871, China. 11PKU-IDG/McGovern Institute for Brain Research, Beijing 100871, China
Kebin Shi (kebinshi@pku.edu.cn)
Liangyi Chen (lychen@pku.edu.cn)
Published:2020,
Published Online:28 January 2020,
Received:06 November 2019,
Revised:11 January 2020,
Accepted:14 January 2020
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Dong, D. S. et al. Super-resolution fluorescence-assisted diffraction computational tomography reveals the three-dimensional landscape of the cellular organelle interactome. Light: Science & Applications, 9, 99–113 (2020).
Dong, D. S. et al. Super-resolution fluorescence-assisted diffraction computational tomography reveals the three-dimensional landscape of the cellular organelle interactome. Light: Science & Applications, 9, 99–113 (2020). DOI: 10.1038/s41377-020-0249-4.
The emergence of super-resolution (SR) fluorescence microscopy has rejuvenated the search for new cellular sub-structures. However
SR fluorescence microscopy achieves high contrast at the expense of a holistic view of the interacting partners and surrounding environment. Thus
we developed SR fluorescence-assisted diffraction computational tomography (SR-FACT)
which combines label-free three-dimensional optical diffraction tomography (ODT) with two-dimensional fluorescence Hessian structured illumination microscopy. The ODT module is capable of resolving the mitochondria
lipid droplets
the nuclear membrane
chromosomes
the tubular endoplasmic reticulum
and lysosomes. Using dual-mode correlated live-cell imaging for a prolonged period of time
we observed novel subcellular structures named dark-vacuole bodies
the majority of which originate from densely populated perinuclear regions
and intensively interact with organelles such as the mitochondria and the nuclear membrane before ultimately collapsing into the plasma membrane. This work demonstrates the unique capabilities of SR-FACT
which suggests its wide applicability in cell biology in general.
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