Profiling single cancer cell metabolism via high-content SRS imaging with chemical sparsity

Yuying Tan1, Haonan Lin1, Ji-Xin Cheng1,2,3

  • 1Biomedical Engineering, Boston University, Boston, MA 02155, USA.

Science Advances
|August 16, 2023
PubMed

Insights

Scientists developed a new imaging method to map multiple metabolites within single cancer cells. This technique reveals how cancer cells change their metabolism to resist chemotherapy, aiding the search for new treatments.

Area of Science:

  • Biomedical Imaging
  • Chemical Biology
  • Cancer Research

Background:

  • Metabolic reprogramming is key to cancer cell chemoresistance.
  • Current single-cell metabolic profiling methods lack the ability to detect multiple metabolites simultaneously.

Purpose of the Study:

  • To develop a novel high-content imaging approach for simultaneous single-cell metabolic profiling.
  • To investigate chemotherapy-induced metabolic reprogramming and chemoresistance in cancer cells.

Main Methods:

  • Utilized hyperspectral stimulated Raman scattering (hSRS) imaging in the C-H window.
  • Employed sparsity-driven hyperspectral image decomposition for data analysis.
  • Developed a high-content hSRS (h²SRS) imaging technique for simultaneous mapping of five major biomolecules (proteins, carbohydrates, fatty acids, cholesterol, nucleic acids).

Main Results:

  • Successfully mapped five major biomolecules at the single-cell level using h²SRS.
  • Observed acute and adapted metabolic reprogramming in brain and pancreatic cancer cells during chemotherapy.
  • Identified unique metabolic features associated with chemoresistance.

Conclusions:

  • The h²SRS imaging approach enables high-content, label-free chemical imaging of single-cell metabolic profiles.
  • This method can reveal metabolic adaptations driving cancer chemoresistance.
  • The findings are expected to facilitate the discovery of novel therapeutic targets to overcome chemoresistance.