Evidence map›Paper›PMID 36038771›Full record

ArticleNature biomedical engineering2022

Revealing nanostructures in brain tissue via protein decrowding by iterative expansion microscopy.

Deblina Sarkar, Jinyoung Kang, Asmamaw T Wassie, Margaret E Schroeder, Zhuyu Peng, Tyler B Tarr, Ai-Hui Tang, Emily D Niederst, Jennie Z Young, Hanquan Su and 5 more

Open access · greenAbstract read
In one paragraph

Article in Nature biomedical engineering, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed
20.3field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

57 citing papers in PubMed, 83 citations in OpenAlex.

  1. ONE microscopy.Nature protocols · 2026
    Review
  2. Review
  3. Thousandfold Expansion Microscopy.bioRxiv : the preprint server for biology · 2026
    Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Organization of Myosin H in the Apical Complex ofbioRxiv : the preprint server for biology · 2026
    Article
  9. Article
  10. Article
  11. Review
  12. Principles ofbioRxiv : the preprint server for biology · 2026
    Article
  13. Discovery of Abundant Nano-scale Lymphatic-like Vessels in Brains.bioRxiv : the preprint server for biology · 2026
    Article
  14. Article
  15. Review
  16. Article
  17. Review
  18. Nanoscopic Mapping of the Extracellular Space in Amyloid Plaque-rich Cortex.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 8 institutions in 3 countries.

Deblina Sarkar *Media Lab, MIT, Cambridge, MA, USA.ORCID 0000-0002-9662-1666
Jinyoung Kang *MIT McGovern Institute for Brain Research, MIT, Cambridge, MA, USA.
Asmamaw T Wassie *Department of Biological Engineering, MIT, Cambridge, MA, USA.
Margaret E SchroederMIT McGovern Institute for Brain Research, MIT, Cambridge, MA, USA.
Zhuyu PengDepartment of Brain and Cognitive Sciences, MIT, Cambridge, MA, USA.
Tyler B TarrDepartment of Physiology, University of Maryland School of Medicine, Baltimore, MD, USA.
Ai-Hui TangDepartment of Physiology, University of Maryland School of Medicine, Baltimore, MD, USA.
Emily D NiederstThe Picower Institute for Learning and Memory, MIT, Cambridge, MA, USA.
Jennie Z YoungDepartment of Brain and Cognitive Sciences, MIT, Cambridge, MA, USA.
Hanquan SuWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.ORCID 0000-0002-5029-580X
Demian ParkMIT McGovern Institute for Brain Research, MIT, Cambridge, MA, USA.
Peng YinWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.
Li-Huei TsaiDepartment of Brain and Cognitive Sciences, MIT, Cambridge, MA, USA. lhtsai@mit.edu.ORCID 0000-0003-1262-0592
Thomas A BlanpiedDepartment of Physiology, University of Maryland School of Medicine, Baltimore, MD, USA. TBlanpied@som.umaryland.edu.ORCID 0000-0003-4957-557X
Edward S BoydenMIT Center for Neurobiological Engineering, MIT, Cambridge, MA, USA. edboyden@mit.edu.ORCID 0000-0002-0419-3351
McGovern Institute for Brain Research · USHarvard University · USUniversity of Maryland, Baltimore · USBroad Institute · USHoward Hughes Medical Institute · USHuman Media · USIIT@MIT · USUniversity of Science and Technology of China · CN

Funding

Center for Genomically Engineered OrgansRM1HG008525 · NHGRI · HARVARD MEDICAL SCHOOL · PI CHURCH, GEORGE M · 2015 to 2019
$10.2M
Recombinant Immunolabels for Nanoprecise Brain Mapping Across ScalesU24NS109113 · NINDS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI KARL Daniel MURRAY · 2018 to 2026
$9.9M
High-throughput single-molecule protein identification via super-resolution imagingDP1GM133052 · NIGMS · HARVARD UNIVERSITY · PI YIN, PENG · 2018 to 2022
$6.6M
Internal Dynamics of the Postsynaptic DensityR37MH080046 · NIMH · UNIVERSITY OF MARYLAND BALTIMORE · PI Thomas A Blanpied · 2020 to 2026
$5.0M
Expansion MicroscopyR01EB024261 · NIBIB · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BOYDEN, EDWARD S. · 2017 to 2025
$4.6M
Demystifying Microglia in Aging and Alzheimer's DiseaseRF1AG054321 · NIA · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI DE JAGER, PHILIP L, LEVIN, JOSHUA ZVI · 2016 to 2016
$4.0M
Millisecond-Timescale Whole-Brain Neural Activity Mapping in Health and DiseaseDP1NS087724 · NINDS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BOYDEN, EDWARD S. · 2013 to 2017
$3.9M
Mechanisms of pathology and neuronal hyperactivity in a memory circuit in Alzheimer's diseaseR01AG070831 · NIA · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BOYDEN, EDWARD S., TSAI, LI-HUEI · 2021 to 2025
$3.2M
An Accessible Optical Toolbox for Saturated Nanoscale Analysis of Neural ArchitectureR01MH110932 · NIMH · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BOYDEN, EDWARD S., CAI, DAWEN · 2016 to 2019
$2.8M
Dynamic control of synapse organization and function by cleft-resident moleculesR01MH119826 · NIMH · YALE UNIVERSITY · PI BIEDERER, THOMAS, BLANPIED, THOMAS A · 2019 to 2023
$2.8M
Multiplexed Nanoscale Protein Mapping Through Expansion Microscopy and Immuno-SABERRF1MH124606 · NIMH · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BOYDEN, EDWARD S., YIN, PENG · 2020 to 2020
$2.7M
Mechanisms underlying DNA double strand break response in Alzheimer?s disease and frontal temporal dementiaR01NS102730 · NINDS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI TSAI, LI-HUEI · 2017 to 2021
$2.1M
Howard Hughes Medical InstituteNHGRI NIH HHS RM1 HG008525NIA NIH HHS R01 AG070831NIA NIH HHS R56 AG069192NIA NIH HHS RF1 AG054321NIBIB NIH HHS R01 EB024261NIGMS NIH HHS DP1 GM133052NIGMS NIH HHS K99 GM126277NIGMS NIH HHS R00 GM126277NIMH NIH HHS R01 MH110932NIMH NIH HHS R01 MH119826NIMH NIH HHS R37 MH080046NIMH NIH HHS RF1 MH124606NINDS NIH HHS DP1 NS087724NINDS NIH HHS R01 NS102730NINDS NIH HHS U24 NS109113
6 · The paper itself

Abstract

Many crowded biomolecular structures in cells and tissues are inaccessible to labelling antibodies. To understand how proteins within these structures are arranged with nanoscale precision therefore requires that these structures be decrowded before labelling. Here we show that an iterative variant of expansion microscopy (the permeation of cells and tissues by a swellable hydrogel followed by isotropic hydrogel expansion, to allow for enhanced imaging resolution with ordinary microscopes) enables the imaging of nanostructures in expanded yet otherwise intact tissues at a resolution of about 20 nm. The method, which we named 'expansion revealing' and validated with DNA-probe-based super-resolution microscopy, involves gel-anchoring reagents and the embedding, expansion and re-embedding of the sample in homogeneous swellable hydrogels. Expansion revealing enabled us to use confocal microscopy to image the alignment of pre-synaptic calcium channels with post-synaptic scaffolding proteins in intact brain circuits, and to uncover periodic amyloid nanoclusters containing ion-channel proteins in brain tissue from a mouse model of Alzheimer's disease. Expansion revealing will enable the further discovery of previously unseen nanostructures within cells and tissues.

Indexed as

MicroscopyNanostructuresAnimalsBrainCalcium ChannelsDNAHydrogelsMiceProteinsCalcium ChannelsDNAHydrogelsProteins

Identifiers

PMID36038771
PMCPMC9551354
OpenAlexW4293475074

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.