Protection of tissue physicochemical properties using polyfunctional crosslinkers

Young Gyun Park, Chang Ho Sohn, Ritchie Chen, Margaret McCue, Dae Hee Yun, Gabrielle T. Drummond, Taeyun Ku, Nicholas B. Evans, Hayeon Caitlyn Oak, Wendy Trieu, Heejin Choi, Xin Jin, Varoth Lilascharoen, Ji Wang, Matthias C. Truttmann, Helena W. Qi, Hidde L. Ploegh, Todd R. Golub, Shih Chi Chen, Matthew P. FroschHeather J. Kulik, Byung Kook Lim, Kwanghun Chung

Research output: Contribution to journalArticle

21 Citations (Scopus)

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.

Original languageEnglish
Number of pages1
JournalNature Biotechnology
Volume37
Issue number1
DOIs
Publication statusPublished - 2019 Jan 1

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology
  • Molecular Medicine
  • Biomedical Engineering

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  • Cite this

    Park, Y. G., Sohn, C. H., Chen, R., McCue, M., Yun, D. H., Drummond, G. T., Ku, T., Evans, N. B., Oak, H. C., Trieu, W., Choi, H., Jin, X., Lilascharoen, V., Wang, J., Truttmann, M. C., Qi, H. W., Ploegh, H. L., Golub, T. R., Chen, S. C., ... Chung, K. (2019). Protection of tissue physicochemical properties using polyfunctional crosslinkers. Nature Biotechnology, 37(1). https://doi.org/10.1038/nbt.4281