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Light microscopy of proteins in their ultrastructural context

Author

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  • Ons M’Saad

    (Yale School of Medicine
    Yale University)

  • Joerg Bewersdorf

    (Yale School of Medicine
    Yale University
    Kavli Institute for Neuroscience, Yale School of Medicine
    Nanobiology Institute, Yale University)

Abstract

Resolving the distribution of specific proteins at the nanoscale in the ultrastructural context of the cell is a major challenge in fluorescence microscopy. We report the discovery of a new principle for an optical contrast equivalent to electron microscopy (EM) which reveals the ultrastructural context of the cells with a conventional confocal microscope. By decrowding the intracellular space through 13 to 21-fold physical expansion while simultaneously retaining the proteins, bulk (pan) labeling of the proteome resolves local protein densities and reveals the cellular nanoarchitecture by standard light microscopy.

Suggested Citation

  • Ons M’Saad & Joerg Bewersdorf, 2020. "Light microscopy of proteins in their ultrastructural context," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17523-8
    DOI: 10.1038/s41467-020-17523-8
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    Cited by:

    1. Ravish Rashpa & Natacha Klages & Domitille Schvartz & Carla Pasquarello & Mathieu Brochet, 2023. "The Skp1-Cullin1-FBXO1 complex is a pleiotropic regulator required for the formation of gametes and motile forms in Plasmodium berghei," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    2. Lingli Kong & Jianfang Liu & Meng Zhang & Zhuoyang Lu & Han Xue & Amy Ren & Jiankang Liu & Jinping Li & Wai Li Ling & Gang Ren, 2023. "Facile hermetic TEM grid preparation for molecular imaging of hydrated biological samples at room temperature," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    3. Vincent Louvel & Romuald Haase & Olivier Mercey & Marine H. Laporte & Thibaut Eloy & Étienne Baudrier & Denis Fortun & Dominique Soldati-Favre & Virginie Hamel & Paul Guichard, 2023. "iU-ExM: nanoscopy of organelles and tissues with iterative ultrastructure expansion microscopy," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    4. Zhen Dong & Wenhao Jiang & Chunlong Wu & Ting Chen & Jiayi Chen & Xuan Ding & Shu Zheng & Kiryl D. Piatkevich & Yi Zhu & Tiannan Guo, 2024. "Spatial proteomics of single cells and organelles on tissue slides using filter-aided expansion proteomics," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    5. Alexander A. Morano & Rachel M. Rudlaff & Jeffrey D. Dvorin, 2023. "A PPP-type pseudophosphatase is required for the maintenance of basal complex integrity in Plasmodium falciparum," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

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