TY - JOUR T1 - Multi-color 4D superresolution light-sheet microscopy reveals organelle interactions at isotropic 100-nm resolution and sub-second timescales JF - bioRxiv DO - 10.1101/2021.05.09.443230 SP - 2021.05.09.443230 AU - Yuxuan Zhao AU - Meng Zhang AU - Wenting Zhang AU - Qing Liu AU - Peng Wang AU - Rong Chen AU - Peng Fei AU - Yu-Hui Zhang Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/05/10/2021.05.09.443230.abstract N2 - Long-term visualization of the dynamic organelle-organelle or protein-organelle interactions throughout the three-dimensional space of whole live cells is essential to better understand their functions, but this task remains challenging due to the limitations of existing three-dimensional fluorescence microscopy techniques, such as an insufficient axial resolution, low volumetric imaging rate, and photobleaching. Here, we present the combination of a progressive deep-learning superresolution strategy with a dual-ring-modulated SPIM design capable of visualizing the dynamics of intracellular organelles in live cells for hours at an isotropic spatial resolution of ~100 nm in three dimensions and a temporal resolution up to ~17 Hz. With a compelling spatiotemporal resolution, we substantially reveal the complex spatial relationships and interactions between the endoplasmic reticulum (ER) and mitochondria throughout live cells, providing new insights into ER-mediated mitochondrial division. We also localized the motion of Drp1 oligomers in three dimensions and observed Drp1-mediated mitochondrial branching for the first time.Competing Interest StatementThe authors have declared no competing interest. ER -