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dc.contributor.authorSarkar, Deblina
dc.contributor.authorKang, Jinyoung
dc.contributor.authorWassie, Asmamaw T
dc.contributor.authorSchroeder, Margaret E
dc.contributor.authorPeng, Zhuyu
dc.contributor.authorTarr, Tyler B
dc.contributor.authorTang, Ai-Hui
dc.contributor.authorNiederst, Emily D
dc.contributor.authorYoung, Jennie Z
dc.contributor.authorSu, Hanquan
dc.contributor.authorPark, Demian
dc.contributor.authorYin, Peng
dc.contributor.authorTsai, Li-Huei
dc.contributor.authorBlanpied, Thomas A
dc.contributor.authorBoyden, Edward S
dc.date.accessioned2023-03-07T16:44:59Z
dc.date.available2023-03-07T16:44:59Z
dc.date.issued2022
dc.identifier.urihttps://hdl.handle.net/1721.1/148392
dc.description.abstractMany 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.en_US
dc.language.isoen
dc.publisherSpringer Science and Business Media LLCen_US
dc.relation.isversionof10.1038/S41551-022-00912-3en_US
dc.rightsCreative Commons Attribution-Noncommercial-Share Alikeen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/en_US
dc.sourcePMCen_US
dc.titleRevealing nanostructures in brain tissue via protein decrowding by iterative expansion microscopyen_US
dc.typeArticleen_US
dc.identifier.citationSarkar, Deblina, Kang, Jinyoung, Wassie, Asmamaw T, Schroeder, Margaret E, Peng, Zhuyu et al. 2022. "Revealing nanostructures in brain tissue via protein decrowding by iterative expansion microscopy." Nature Biomedical Engineering, 6 (9).
dc.contributor.departmentMassachusetts Institute of Technology. Media Laboratory
dc.contributor.departmentMcGovern Institute for Brain Research at MIT
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biological Engineering
dc.contributor.departmentMassachusetts Institute of Technology. Department of Brain and Cognitive Sciences
dc.contributor.departmentPicower Institute for Learning and Memory
dc.contributor.departmentKoch Institute for Integrative Cancer Research at MIT
dc.contributor.departmentHoward Hughes Medical Institute
dc.contributor.departmentProgram in Media Arts and Sciences (Massachusetts Institute of Technology)
dc.relation.journalNature Biomedical Engineeringen_US
dc.eprint.versionAuthor's final manuscripten_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dc.date.updated2023-03-07T16:26:02Z
dspace.orderedauthorsSarkar, D; Kang, J; Wassie, AT; Schroeder, ME; Peng, Z; Tarr, TB; Tang, A-H; Niederst, ED; Young, JZ; Su, H; Park, D; Yin, P; Tsai, L-H; Blanpied, TA; Boyden, ESen_US
dspace.date.submission2023-03-07T16:26:07Z
mit.journal.volume6en_US
mit.journal.issue9en_US
mit.licenseOPEN_ACCESS_POLICY
mit.metadata.statusAuthority Work and Publication Information Neededen_US


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