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In Situ 3D Super Resolution Nanoscale Imaging of Cell Spheroids by Expansion Microscopy
Junfang Xie1,2, Yifei Zhan1, Jin Wang1
1Key Laboratory of Weak-Light Nonlinear Photonics, Ministry of Education, School of Physics and TEDA Applied Physics, Nankai University, Tianjin, China.
Journal of Biophotonics
|March 17, 2026
Summary
Researchers developed a 3D cell model using gelatin methacryloyl (GelMA) hydrogels for enhanced drug screening. This model allows high-resolution imaging of subcellular structures like mitochondria within cell spheroids.
Area of Science:
- Biomedical Engineering
- Cell Biology
- Drug Discovery
Background:
- Three-dimensional (3D) cell models offer improved physiological relevance for drug screening.
- Subcellular structure visualization in 3D models is hindered by light scattering.
Purpose of the Study:
- To develop a 3D HeLa cell spheroid model in GelMA hydrogel for advanced drug screening.
- To enable high-resolution, in situ imaging of subcellular structures within 3D cell spheroids.
Main Methods:
- Cultured 3D HeLa cell spheroids within gelatin methacryloyl (GelMA) hydrogels.
- Implemented a 4.6-fold expansion protocol for enhanced imaging.
- Utilized a commercial confocal microscope for high-resolution imaging (approx. 90 nm).
Main Results:
- Achieved unprecedented, in situ visualization of individual mitochondrial morphology within 3D cell spheroids.
- Quantitatively analyzed drug-induced changes in mitochondrial morphology.
- Established a high-content 3D cell model for drug screening.
Conclusions:
- The developed GelMA-based 3D cell model facilitates high-resolution subcellular imaging.
- This method deepens the understanding of drug mechanisms in a physiologically relevant context.
- Enables advanced drug screening with improved resolution and detail.
