Single-Cell SERS Imaging Reveals Lipid-Associated Water Metabolism and Dormant Tumor Cell Signatures in Living Cancer Cells, Ruiyao Ma Study of Cellular Water Metabolism

Research Hypothesis
This study hypothesized that integrating surface-enhanced Raman scattering (SERS), deuterium oxide (D₂O) labeling, and a custom micropore chip would enable real-time, high-resolution visualization of intracellular water metabolism. It aimed to distinguish metabolic differences between cancer/normal cells and metastatic/dormant tumor cells, identify subcellular water metabolic hubs, and monitor cisplatin (CDDP)-induced metabolic changes.
Data Collection
Platform: Micropore chips (32 μm diameter, 25 μm depth) coated with 200 nm Ag and 100 nm Au, achieving an enhancement factor (EF) of 1.18×10⁴ vs. glass slides.
Cells: Normal (H8), cervical cancer (HeLa), metastatic (H1915-BrM), and dormant (H1915-DM) cells, cultured in D₂O-containing medium (D-DMEM) or treated with 1 mM CDDP.
Imaging: 2D/3D SERS imaging (532 nm laser) at 0–48 h; data processed via Lorentzian fitting, 7 similarity algorithms (e.g., SNR, pHash), and PCA.
Key Findings
1. Cancer cells (HeLa) showed faster D₂O uptake and higher C-D signal intensity than normal cells (H8), with a 48-hour metabolic cycle.
2. Lipid-rich cytoplasmic regions were primary water metabolic hotspots, with C-D signals strongly correlating with lipids (2840–2870 cm⁻¹) and weakly with DNA.
3. CDDP suppressed water metabolism, reduced DNA content (785 cm⁻¹ peak), and altered lipid/protein metabolism (1446, 2892 cm⁻¹ peaks).
4. Dormant cells (H1915-DM) exhibited low but sustained water metabolism, elevated proline/tyrosine, and resistance to CDDP, unlike metastatic cells (H1915-BrM).
Interpretation
C-D bond intensity reflects water incorporation into biomolecules, with lipid-rich regions driving metabolic water exchange. The platform resolves subcellular and single-cell heterogeneity, enabling drug response monitoring and dormant cell identification. It offers a non-invasive tool for studying tumor metabolism and developing precision therapies.