ArticleProceedings of the National Academy of Sciences of the United States of America2019
Cryo-SOFI enabling low-dose super-resolution correlative light and electron cryo-microscopy.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed.
- Mitochondrial-endoplasmic reticulum interactions in lung diseases.Cell death & disease · 2026Review
- Integrated fluorescence light microscopy-guided cryo-focused ion beam-milling for in situ montage cryo-ET.Nature protocols · 2026Review
- Subcellular chemical mapping using correlated cryogenic electron and mass spectrometry imaging.Nature methods · 2026Article
- A cryo-CLEM-guided workflow for quantitative assessment and optimization of cryo-ET specimen quality.Molecules and cells · 2026Article
- Combining Correlative Cryogenic Fluorescence and Electron Microscopy and Correlative Cryogenic Super-Resolution Fluorescence and X-Ray Tomography-Novel Complementary 3D Cryo-Microscopy Across Scales to Reveal Nanoparticle Internalization Into Cancer Cells.Microscopy research and technique · 2026Article
- Visualizing Postsynaptic Density in Excitatory Synapses with Electron Tomography.Advances in neurobiology · 2026Review
- Deciphering Cellular Intricacies for Drug Discovery: A Synergistic Approach Combining Cryo-CLEM, Electromechanical Modeling, a nd AI-Guided Simulations.Combinatorial chemistry & high throughput screening · 2026Article
- Determination of factors that allow cryogenic nanoscopy with high power illumination without devitrification.PloS one · 2026Article
- Molecular tags for electron cryo-tomography.Emerging topics in life sciences · 2025Review
- There and back again: a cell biologist's journey from organelles to molecules.Biological chemistry · 2025Review
- Cryogenic light microscopy of vitrified samples with angstrom precision.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Mechanisms of COPII coat assembly and cargo recognition in the secretory pathway.Nature reviews. Molecular cell biology · 2025Review
- Demonstrating soft X-ray tomography in the lab for correlative cryogenic biological imaging using X-rays and light microscopy.Scientific reports · 2025Article
- Time-deterministic cryo-optical microscopy.Light, science & applications · 2025Article
- Super-resolution microscopy for structural biology.Nature methods · 2025Review
- Cryogenic single-molecule fluorescence imaging.BMB reports · 2025Review
- Recent advances in correlative cryo-light and electron microscopy.Current opinion in structural biology · 2024Review
- Cross-Correlation Increases Sampling in Diffusion-Based Super-Resolution Optical Fluctuation Imaging.Chemical & biomedical imaging · 2024Article
- Honeycomb gold specimen supports enabling orthogonal focussed ion beam-milling of elongated cells for cryo-ET.Journal of structural biology · 2024Article
- Combining per-particle cryo-ET and cryo-EM single particle analysis to elucidate heterogeneous DNA-protein organization.Current opinion in structural biology · 2024Review
Corrections and comments
- Erratum issued
Authors and funding
8 authors.
Funding
Abstract
Correlative light and electron cryo-microscopy (cryo-CLEM) combines information from the specific labeling of fluorescence cryo-microscopy (cryo-FM) with the high resolution in environmental context of electron cryo-microscopy (cryo-EM). Exploiting super-resolution methods for cryo-FM is advantageous, as it enables the identification of rare events within the environmental background of cryo-EM at a sensitivity and resolution beyond that of conventional methods. However, due to the need for relatively high laser intensities, current super-resolution cryo-CLEM methods require cryo-protectants or support films which can severely reduce image quality in cryo-EM and are not compatible with many samples, such as mammalian cells. Here, we introduce cryogenic super-resolution optical fluctuation imaging (cryo-SOFI), a low-dose super-resolution imaging scheme based on the SOFI principle. As cryo-SOFI does not require special sample preparation, it is fully compatible with conventional cryo-EM specimens, and importantly, it does not affect the quality of cryo-EM imaging. By applying cryo-SOFI to a variety of biological application examples, we demonstrate resolutions up to ∼135 nm, an improvement of up to three times compared with conventional cryo-FM, while maintaining the specimen in a vitrified state for subsequent cryo-EM. Cryo-SOFI presents a general solution to the problem of specimen devitrification in super-resolution cryo-CLEM. It does not require a complex optical setup and can easily be implemented in any existing cryo-FM system.
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