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Protection of tissue physicochemical properties using polyfunctional crosslinkers

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; Choi, Heejin; Jin, Xin; Lilascharoen, Varoth; Wang, Ji; Truttmann, Matthias C; Qi, Helena Wen; Ploegh, Hidde L; Golub, Todd R; Chen, Shih-Chi; Frosch, Matthew P; Kulik, Heather Janine; Lim, Byung Kook; Chung, Kwanghun; ... Show more Show less
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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.
Date issued
2018-12
URI
https://hdl.handle.net/1721.1/128842
Department
Massachusetts Institute of Technology. Institute for Medical Engineering and 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
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
ISSN
1087-0156
1546-1696

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