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Protection of tissue physicochemical properties using polyfunctional crosslinkers
Young-Gyun Park1,2, Chang Ho Sohn1,2, Ritchie Chen1,2
1Institute for Medical Engineering and Science, Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, USA.
Nature Biotechnology
|December 18, 2018
Summary
A new tissue preservation method called SHIELD protects biomolecules and tissue structure from damage. This allows for detailed, system-wide analysis of molecular and cellular features in various tissues.
Area of Science:
- Biotechnology
- Molecular Biology
- Tissue Engineering
Background:
- Characterizing complex biological systems requires system-wide molecular and cellular data.
- Current spatial mapping methods for biomolecules in tissues cause information loss due to degradation and damage.
Purpose of the Study:
- To develop a novel tissue transformation strategy to preserve biomolecules and tissue architecture.
- To enable high-resolution, system-wide analysis of molecular and cellular features in intact tissues.
Main Methods:
- Introduced SHIELD (stabilization under harsh conditions via intramolecular epoxide linkages to prevent degradation), a method using a flexible polyepoxide for cross-linking biomolecules.
- Applied SHIELD to preserve protein fluorescence, antigenicity, transcripts, and tissue architecture under harsh conditions.
Main Results:
- SHIELD successfully preserved molecular and structural integrity in various harsh conditions.
- Demonstrated single-cell resolution analysis of neural circuits and synaptic architecture in mouse models.
- Enabled rapid 3D phenotyping of core needle biopsies and human brain cells.
Conclusions:
- SHIELD is a versatile strategy for preserving diverse tissue types, including animal and clinical samples.
- This method facilitates rapid, multiscale, integrated molecular phenotyping for comprehensive biological system analysis.
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