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Multiplexed expansion revealing for imaging multiprotein nanostructures in healthy and diseased brain

Author

Listed:
  • Jinyoung Kang

    (MIT
    MIT)

  • Margaret E. Schroeder

    (MIT
    MIT)

  • Youngmi Lee

    (MIT)

  • Chaitanya Kapoor

    (Department of Electrical and Electronics Engineering)

  • Eunah Yu

    (MIT)

  • Tyler B. Tarr

    (University of Pittsburgh)

  • Kat Titterton

    (MIT)

  • Menglong Zeng

    (MIT)

  • Demian Park

    (MIT)

  • Emily Niederst

    (MIT)

  • Donglai Wei

    (Boston College)

  • Guoping Feng

    (MIT
    MIT
    MIT
    Broad Institute of MIT and Harvard)

  • Edward S. Boyden

    (MIT
    MIT
    MIT
    MIT)

Abstract

Proteins work together in nanostructures in many physiological contexts and disease states. We recently developed expansion revealing (ExR), which expands proteins away from each other, in order to support better labeling with antibody tags and nanoscale imaging on conventional microscopes. Here, we report multiplexed expansion revealing (multiExR), which enables high-fidelity antibody visualization of >20 proteins in the same specimen, over serial rounds of staining and imaging. Across all datasets examined, multiExR exhibits a median round-to-round registration error of 39 nm, with a median registration error of 25 nm when the most stringent form of the protocol is used. We precisely map 23 proteins in the brain of 5xFAD Alzheimer’s model mice, and find reductions in synaptic protein cluster volume, and co-localization of specific AMPA receptor subunits with amyloid-beta nanoclusters. We visualize 20 synaptic proteins in specimens of mouse primary somatosensory cortex. multiExR may be of broad use in analyzing how different kinds of protein are organized amidst normal and pathological processes in biology.

Suggested Citation

  • Jinyoung Kang & Margaret E. Schroeder & Youngmi Lee & Chaitanya Kapoor & Eunah Yu & Tyler B. Tarr & Kat Titterton & Menglong Zeng & Demian Park & Emily Niederst & Donglai Wei & Guoping Feng & Edward S, 2024. "Multiplexed expansion revealing for imaging multiprotein nanostructures in healthy and diseased brain," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53729-w
    DOI: 10.1038/s41467-024-53729-w
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    References listed on IDEAS

    as
    1. Maja Klevanski & Frank Herrmannsdoerfer & Steffen Sass & Varun Venkataramani & Mike Heilemann & Thomas Kuner, 2020. "Automated highly multiplexed super-resolution imaging of protein nano-architecture in cells and tissues," Nature Communications, Nature, vol. 11(1), pages 1-11, December.
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    3. Hunter F. Iaccarino & Annabelle C. Singer & Anthony J. Martorell & Andrii Rudenko & Fan Gao & Tyler Z. Gillingham & Hansruedi Mathys & Jinsoo Seo & Oleg Kritskiy & Fatema Abdurrob & Chinnakkaruppan Ad, 2016. "Gamma frequency entrainment attenuates amyloid load and modifies microglia," Nature, Nature, vol. 540(7632), pages 230-235, December.
    4. Fred Y. Shen & Margaret M. Harrington & Logan A. Walker & Hon Pong Jimmy Cheng & Edward S. Boyden & Dawen Cai, 2020. "Light microscopy based approach for mapping connectivity with molecular specificity," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
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