Visualizing intraorganellar ultrastructures, dynamics, and interactions with open-access background-free Lock-in-SIM

Structured illumination microscopy (SIM) is a powerful method for fast and gentle live-cell super-resolution imaging. However, its susceptibility to reconstruction artifacts from out-of-focus blur and background imposes substantial barriers to analyze the dynamics of densely packed volumetric intraorganellar ultrastructures that are typically in a size range of SIM's spatial resolution. To address this limitation, we have developed Lock-in-SIM, an open-access two-dimensional SIM framework that eliminates background and maximizes the recovery of sub-diffraction information with the highest possible frequency extraction. By leveraging the intrinsic modulation differences of volumetric sample structures, Lock-in-SIM enables efficient optical sectioning, extends imaging depth, and improves data fidelity and quantifiability. We demonstrate the superiority of Lock-in-SIM by visualizing various challenging intraorganellar ultrastructures in live cells. Our investigations uncover mechanisms of mitochondrial fission and endoplasmic reticulum-lysosome interactions and provide insights into the intricate yet highly regulated structural remodeling of organelles.

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Publication Details

Journal
Nature Communications
Published
2025-11-28
DOI
https://doi.org/10.1038/s41467-025-65805-w
Primary Topic
Advanced Fluorescence Microscopy Techniques
Type
article
Field-Weighted Citation Impact
0.00

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article

Visualizing intraorganellar ultrastructures, dynamics, and interactions with open-access background-free Lock-in-SIM

Wei Yang, Qiuyuan Fang, Wenbin Zhu, Shunyu Xie et al.
Nature Communications
Advanced Fluorescence Microscopy Techniques
article

Visualizing intraorganellar ultrastructures, dynamics, and interactions with open-access background-free Lock-in-SIM

Wei Yang, Qiuyuan Fang, Wenbin Zhu, Shunyu Xie, Shuhao Qian, Dazhao Zhu, Cuifang Kuang, Jianjie Dong, Lothar Schermelleh, Xü Liu, Yì Wáng, Jinfeng Zhang, Wenjie Liu, Meng Zhang, Yuhui Zhang, Zhiyi Liu, Zheng Xiu, Youhua Chen
article en

Abstract

Structured illumination microscopy (SIM) is a powerful method for fast and gentle live-cell super-resolution imaging. However, its susceptibility to reconstruction artifacts from out-of-focus blur and background imposes substantial barriers to analyze the dynamics of densely packed volumetric intraorganellar ultrastructures that are typically in a size range of SIM's spatial resolution. To address this limitation, we have developed Lock-in-SIM, an open-access two-dimensional SIM framework that eliminates background and maximizes the recovery of sub-diffraction information with the highest possible frequency extraction. By leveraging the intrinsic modulation differences of volumetric sample structures, Lock-in-SIM enables efficient optical sectioning, extends imaging depth, and improves data fidelity and quantifiability. We demonstrate the superiority of Lock-in-SIM by visualizing various challenging intraorganellar ultrastructures in live cells. Our investigations uncover mechanisms of mitochondrial fission and endoplasmic reticulum-lysosome interactions and provide insights into the intricate yet highly regulated structural remodeling of organelles.

Nature CommunicationsVol. 16(1)
Ningbo University (CN), University of Oxford (GB), Shanghai Zhangjiang Laboratory (CN), Zhejiang Lab (CN), Wuhan National Laboratory for Optoelectronics (CN), Zhejiang University (CN)
Wellcome Trust, University of Oxford, European Commission, National Natural Science Foundation of China, China Postdoctoral Science Foundation, Huazhong University of Science and Technology, Zhejiang University, Universität Bielefeld, Wuhan National Laboratory for Optoelectronics, National Physical Laboratory, National Key Research and Development Program of China, Natural Science Foundation of Zhejiang Province
Openalex Percentile: Top 74%
Advanced Fluorescence Microscopy Techniques
DOIOpen Access PDFOpenAlex
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