Epitope-preserving magnified analysis of proteome (eMAP)
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sciadv.abf6589.pdf
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Published version
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Author(s) • • • • • • • • •
Park, Joha
Khan, Sarim
Yun, Dae Hee
Ku, Taeyun
Villa, Katherine L
Lee, Jiachen E
Zhang, Qiangge
Park, Juhyuk
Feng, Guoping
Nedivi, Elly
Date Issued
November 12, 2021
Journal
Science Advances
Publisher
American Association for the Advancement of Science (AAAS)
Citation
Park, Joha, Khan, Sarim, Yun, Dae Hee, Ku, Taeyun, Villa, Katherine L et al. 2021. "Epitope-preserving magnified analysis of proteome (eMAP)." Science Advances, 7 (46).
Version
Final published version
Abstract
Synthetic tissue-hydrogel methods have enabled superresolution investigation of biological systems using diffraction-limited microscopy. However, chemical modification by fixatives can cause loss of antigenicity, limiting molecular interrogation of the tissue gel. Here, we present epitope-preserving magnified analysis of proteome (eMAP) that uses purely physical tissue-gel hybridization to minimize the loss of antigenicity while allowing permanent anchoring of biomolecules. We achieved success rates of 96% and 94% with synaptic antibodies for mouse and marmoset brains, respectively. Maximal preservation of antigenicity allows imaging of nanoscopic architectures in 1000-fold expanded tissues without additional signal amplification. eMAP-processed tissue gel can endure repeated staining and destaining without epitope loss or structural damage, enabling highly multiplexed proteomic analysis. We demonstrated the utility of eMAP as a nanoscopic proteomic interrogation tool by investigating molecular heterogeneity in inhibitory synapses in the mouse brain neocortex and characterizing the spatial distributions of synaptic proteins within synapses in mouse and marmoset brains.
MIT Department
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Picower Institute for Learning and Memory
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
McGovern Institute for Brain Research at MIT
Massachusetts Institute of Technology. Department of Chemical Engineering
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Creative Commons Attribution NonCommercial License 4.0
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DOI of Published Version
https://doi.org/10.1126/sciadv.abf6589