Protection of tissue physicochemical properties using polyfunctional crosslinkers
Name
nihms-1508191.pdf
Description
Accepted version
Size
1.65 MB
Format
Adobe PDF
Checksum (MD5)
2810b75744f6a9adbb16c7edd6620b58
Author(s)
Park, Young-Gyun
Sohn, Chang Ho
Chen, Ritchie
McCue, Margaret Grace
Yun, Dae Hee
Drummond, Gabrielle
Ku, Taeyun
Evans, Nicholas B
Oak, Hayeon Caitlyn
Trieu, Wendy
Date Issued
December 2018
Journal
Nature Biotechnology
Publisher
Springer Science and Business Media LLC
Citation
Park, Young-Gyun et al. "Protection of tissue physicochemical properties using polyfunctional crosslinkers." Nature Biotechnology 37, 1 (January 2019): 73–83 © 2019 Nature Publishing Group
Version
Author's final manuscript
Abstract
Understanding complex biological systems requires the system-wide characterization of both molecular and cellular features. Existing methods for spatial mapping of biomolecules in intact tissues suffer from information loss caused by degradation and tissue damage. We report a tissue transformation strategy named stabilization under harsh conditions via intramolecular epoxide linkages to prevent degradation (SHIELD), which uses a flexible polyepoxide to form controlled intra-and intermolecular cross-link with biomolecules. SHIELD preserves protein fluorescence and antigenicity, transcripts and tissue architecture under a wide range of harsh conditions. We applied SHIELD to interrogate system-level wiring, synaptic architecture, and molecular features of virally labeled neurons and their targets in mouse at single-cell resolution. We also demonstrated rapid three-dimensional phenotyping of core needle biopsies and human brain cells. SHIELD enables rapid, multiscale, integrated molecular phenotyping of both animal and clinical tissues.
MIT Department
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Picower Institute for Learning and Memory
Massachusetts Institute of Technology. Department of Chemical Engineering
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Massachusetts Institute of Technology. Department of Chemistry
Terms of Use
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1038/nbt.4281
