A multimodal imaging pipeline to decipher cell-specific metabolic functions and tissue microenvironment dynamics

Area of Science:

• Cellular and Molecular Biology
• Biophysics
• Cancer Research

Background:

• Tissue microenvironments are complex and heterogeneous, making it difficult to study cell-cell metabolic interactions.
• Current techniques lack the resolution and specificity to trace metabolic exchanges between distinct cell types in situ.

Purpose of the Study:

• To describe a novel multimodal imaging pipeline for simultaneous cell type identification and nanoscale metabolic tracing.
• To investigate nutrient uptake by tumor-associated immune cells in cancer models.

Main Methods:

• Combined confocal microscopy (fluorescence) with electron microscopy and nanoscale secondary ion mass spectrometry (nanoSIMS).
• Utilized in vivo fluorescent antibody labeling for cell type identification (B cells, T cells, macrophages).
• Traced stable isotope-labeled compounds (e.g., 13C-glucose, 15N-glutamine) within intracellular compartments.

Main Results:

• Successfully identified specific immune cell populations within tumor microenvironments.
• Quantified the uptake and intracellular localization of stable isotope-labeled nutrients by these cells.
• Demonstrated the pipeline's capability to analyze metabolic interactions at the nanoscale.

Conclusions:

• The developed multimodal imaging pipeline enables detailed analysis of cell-specific metabolic interactions in complex tissues.
• This approach advances the study of cellular metabolism in cancer and other biological systems.
• The pipeline is adaptable for tracing various molecules in different tissue types.