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Visualization of Organelles In Situ by Cryo-STEM Tomography
Published on: June 23, 2023
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Visualizing intraorganellar ultrastructures, dynamics, and interactions with open-access background-free Lock-in-SIM
Wenjie Liu1,2, Meng Zhang3, Wenbin Zhu4
1Department of Biochemistry, University of Oxford, Oxford, UK. wenjie.liu@chem.ox.ac.uk.
Nature Communications
|November 28, 2025
Summary
Lock-in-SIM, a new 2D super-resolution microscopy technique, overcomes background noise and blur to reveal detailed live-cell organelle structures. This advanced imaging method enhances understanding of mitochondrial and ER-lysosome dynamics.
Area of Science:
- Cell Biology
- Microscopy
- Biophysics
Background:
- Structured Illumination Microscopy (SIM) offers fast, gentle live-cell super-resolution imaging.
- SIM is limited by reconstruction artifacts from out-of-focus blur and background.
- Analyzing densely packed intraorganellar ultrastructures is challenging due to SIM's spatial resolution limits.
Purpose of the Study:
- To develop an advanced SIM framework to overcome existing limitations.
- To improve the analysis of challenging intraorganellar ultrastructures in live cells.
- To enhance data fidelity and quantifiability in super-resolution microscopy.
Main Methods:
- Developed Lock-in-SIM, an open-access 2D SIM framework.
- Leveraged intrinsic modulation differences of volumetric sample structures.
- Implemented background elimination and maximized high-frequency extraction for improved resolution.
Main Results:
- Lock-in-SIM enables efficient optical sectioning and extends imaging depth.
- Demonstrated superior visualization of challenging live-cell intraorganellar ultrastructures.
- Achieved enhanced data fidelity and quantifiability compared to conventional SIM.
Conclusions:
- Lock-in-SIM significantly improves super-resolution imaging of complex cellular structures.
- The technique provides new insights into mitochondrial fission and ER-lysosome interactions.
- Advanced SIM imaging aids in understanding organelle structural remodeling mechanisms.
