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

7 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

Fingerprint

Tissue
Biomolecules
Large-Core Needle Biopsy
Degradation
Biopsy
Epoxy Compounds
Biological systems
Electric wiring
Needles
Neurons
Brain
Animals
Stabilization
Fluorescence
Proteins

All Science Journal Classification (ASJC) codes

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

Cite this

Park, Young Gyun ; Sohn, Chang Ho ; Chen, Ritchie ; McCue, Margaret ; Yun, Dae Hee ; Drummond, Gabrielle T. ; Ku, Taeyun ; Evans, Nicholas B. ; Oak, Hayeon Caitlyn ; Trieu, Wendy ; Choi, Heejin ; Jin, Xin ; Lilascharoen, Varoth ; Wang, Ji ; Truttmann, Matthias C. ; Qi, Helena W. ; Ploegh, Hidde L. ; Golub, Todd R. ; Chen, Shih Chi ; Frosch, Matthew P. ; Kulik, Heather J. ; Lim, Byung Kook ; Chung, Kwanghun. / Protection of tissue physicochemical properties using polyfunctional crosslinkers. In: Nature Biotechnology. 2019 ; Vol. 37, No. 1.
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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.",
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Park, YG, Sohn, CH, Chen, R, McCue, M, Yun, DH, Drummond, GT, Ku, T, Evans, NB, Oak, HC, Trieu, W, Choi, H, Jin, X, Lilascharoen, V, Wang, J, Truttmann, MC, Qi, HW, Ploegh, HL, Golub, TR, Chen, SC, Frosch, MP, Kulik, HJ, Lim, BK & Chung, K 2019, 'Protection of tissue physicochemical properties using polyfunctional crosslinkers', Nature Biotechnology, vol. 37, no. 1. https://doi.org/10.1038/nbt.4281

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

In: Nature Biotechnology, Vol. 37, No. 1, 01.01.2019.

Research output: Contribution to journalArticle

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T1 - Protection of tissue physicochemical properties using polyfunctional crosslinkers

AU - Park, Young Gyun

AU - Sohn, Chang Ho

AU - Chen, Ritchie

AU - McCue, Margaret

AU - Yun, Dae Hee

AU - Drummond, Gabrielle T.

AU - Ku, Taeyun

AU - Evans, Nicholas B.

AU - Oak, Hayeon Caitlyn

AU - Trieu, Wendy

AU - Choi, Heejin

AU - Jin, Xin

AU - Lilascharoen, Varoth

AU - Wang, Ji

AU - Truttmann, Matthias C.

AU - Qi, Helena W.

AU - Ploegh, Hidde L.

AU - Golub, Todd R.

AU - Chen, Shih Chi

AU - Frosch, Matthew P.

AU - Kulik, Heather J.

AU - Lim, Byung Kook

AU - Chung, Kwanghun

PY - 2019/1/1

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