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Single-Cell Membrane Molecular Cartography Enabled by Nanoengineered VUV-LDI Mass Spectrometry Imaging
Cong-Lin Zhao1, Ling-Ling Zhao1, Bin Kang1
1State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China.
Analytical Chemistry
|September 8, 2025
Summary
We developed a new mass spectrometry imaging platform to analyze single cell membranes, enabling precise mapping of lipids and proteins. This technology aids in distinguishing cancerous cells by identifying aberrant molecular signatures.
Area of Science:
- Biochemistry
- Analytical Chemistry
- Cell Biology
Background:
- Understanding cell membrane composition at the single-cell level is crucial for disease research, particularly for tumor metastasis.
- Technical challenges include the membrane's nanoscale thickness and low molecular abundance, alongside cytoplasmic interference.
Purpose of the Study:
- To introduce a novel Surface-Assisted Vacuum Ultraviolet Laser Desorption-Ionization Mass Spectrometry Imaging (SAVUVDI-MSI) platform for detailed single-cell membrane analysis.
- To overcome limitations in sensitivity and cytoplasmic interference in current membrane analysis techniques.
Main Methods:
- Development of a SAVUVDI-MSI platform utilizing nanoscale depth profiling for precise single-cell membrane ablation.
- Engineering of VUV-laser-cleavable Au-PEG-FA/Apt nanoprobes for specific target recognition and signal enhancement.
- Simultaneous spatial mapping of phospholipids, cholesterol (label-free), and proteins (nanoprobe-targeted).
Main Results:
- Achieved precise ablation of single-cell membranes with reduced cytoplasmic interference.
- Nanoprobes enhanced target protein signals by 4-10 fold.
- Identified aberrant overexpression of proteins and cholesterol on cancer cell membranes.
- Successfully discriminated between cancerous and normal cells using membrane molecular signatures.
Conclusions:
- The SAVUVDI-MSI platform offers high sensitivity and specificity for analyzing membrane components.
- This technology provides a robust method for nanoprobe-enhanced pathological screening with translational potential.
- Establishes a foundation for in situ monitoring of membrane heterogeneity in pathological processes.
