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Two-Level Spatially Localized Proximity Labeling for Cross-Biological-Hierarchy Measurement and Manipulation.

Liusheng Chen¹, Yiran Li¹, Yuna Guo²

¹State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210023, China.

Angewandte Chemie (International Ed. in English)

|January 13, 2025

Summary

This summary is machine-generated.

This study introduces a two-level proximity labeling (P2L) platform for precise molecular mapping in complex biological systems. P2L enables advanced cell discrimination and targeted cell assembly, offering new insights into cellular interactions.

Keywords:

Cellular assembly Enzymatic cascade Logic computation Proximity labeling Two-level spatial localization

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TurboID-Based Proximity Labeling for In Planta Identification of Protein-Protein Interaction Networks

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Published on: May 17, 2020

Area of Science:

Biochemistry
Molecular Biology
Chemical Biology

Background:

Proximity labeling (PL) is crucial for mapping biomolecular interactions in situ.
Current PL methods are limited by single-hierarchy spatial control, hindering applications in multi-tiered biological systems.

Purpose of the Study:

To develop a two-level spatially localized proximity labeling (P2L) platform for enhanced in situ molecular measurement and manipulation.
To demonstrate P2L's capability in executing two-step logic operations and discriminating cells based on glycosylation levels.

Main Methods:

Introduced an additional enzymatic reaction upstream of an enzyme-based PL reaction.
Targeted two enzymes to markers of different biological hierarchies (cellular and glycan levels).
Integrated P2L with click chemistry for cell assembly and with proteomics for glycan microenvironment profiling.

Main Results:

P2L successfully executed a two-step logic operation and differentiated cells with varying glycosylation in mixed populations.
Enabled site-specific covalent assembly of cells by mounting clickable handles via P2L.
Proteomics profiling of specific glycan microenvironments revealed tumor-cell-surface interactions under immune pressure.

Conclusions:

P2L offers a novel solution for dissecting biological system heterogeneity.
The platform provides new insights for intelligent logic computation, enzyme engineering, and tissue engineering.