Raman-guided subcellular pharmaco-metabolomics for metastatic melanoma cells
Open accessAbstract
Non-invasively probing metabolites within single live cells is highly desired but challenging. Here we utilize Raman spectro-microscopy for spatial mapping of metabolites within single cells, with the specific goal of identifying druggable metabolic susceptibilities from a series of patient-derived melanoma cell lines. Each cell line represents a different characteristic level of cancer cell de-differentiation. First, with Raman spectroscopy, followed by stimulated Raman scattering (SRS) microscopy and transcriptomics analysis, we identify the fatty acid synthesis pathway as a druggable susceptibility for differentiated melanocytic cells. We then utilize hyperspectral-SRS imaging of intracellular lipid droplets to identify a previously unknown susceptibility of lipid mono-unsaturation within de-differentiated mesenchymal cells with innate resistance to BRAF inhibition. Drugging this target leads to cellular apoptosis accompanied by the formation of phase-separated intracellular membrane domains. The integration of subcellular Raman spectro-microscopy with lipidomics and transcriptomics suggests possible lipid regulatory mechanisms underlying this pharmacological treatment. Our method should provide a general approach in spatially-resolved single cell metabolomics studies.
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The drug-resistant U cancer cell state displays increased activity of enzymes promoting the synthesis and uptake of PUFAs such as arachidonic acid and linolenic acid.
“The drug-resistant, U cancer cell state displays increased activity of enzymes promoting the synthesis and uptake of PUFAs (16, 17), such as arachidonic acid (AA, C20:4) and linolenic acid (C18:2), which are major substrates for ROS attack.”
From Secreted Apoe rewires melanoma cell state vulnerability to ferroptosis (2024) · cites this paper as [16]
The Discussion (page unavailable) reports upregulated lipid-unsaturation-associated activity in drug-resistant mesenchymal M381 cells, and the Results section on desaturases shows that a PUFA-synthesis enzyme contributes to their lipid-droplet unsaturation. But the Discussion says M381 had the lowest relative lipid-uptake activity, not increased uptake. The desaturases Results section also identifies C18:2 as linoleic acid, not linolenic acid. (LLM, conf=0.88)
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Fluorescence-Detected Mid-Infrared Photothermal Microscopy
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Lipid metabolic Reprogramming: Role in Melanoma Progression and Therapeutic Perspectives
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Stimulated Raman photothermal microscopy toward ultrasensitive chemical imaging
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Quantitative Stimulated Raman Scattering Microscopy: Promises and Pitfalls
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Miniaturized Chemical Tags for Optical Imaging
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Recent Advances in Enhancement of Raman Scattering Intensity for Biological Applications
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Pinpointing Fat Molecules: Advances in Coherent Raman Scattering Microscopy for Lipid Metabolism
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The Raman Map of the Human Cell
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Integrative metabolic flux analysis reveals an indispensable dimension of phenotypes
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Emerging Approaches for Studying Lipid Dynamics, Metabolism, and Interactions in Cells
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Analytical Techniques for Single-Cell Biochemical Assays of Lipids
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Improved ensemble learning enhanced serum fingerprinting spectroscopy for lung cancer diagnosis
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Design Principles Of Inorganic‐Protein Hybrid Materials for Biomedicine
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Genomic Mysteries of Giant Bacteria: Insights and Implications
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Confocal Raman microspectral analysis and imaging of the drug response of osteosarcoma to cisplatin
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Chemical Approaches for Measuring and Manipulating Lipids at the Organelle LevelPreprint
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Signaling and transcriptional dynamics underlying early adaptation to oncogenic BRAF inhibition
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Self-citationSingle-Molecule Vibrational Thermometry
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Self-citationCrosstalk between COVID-19 Infection and Kidney Diseases: A Review on the Metabolomic Approaches
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Upregulated Palmitoleate and Oleate Production in Escherichia coli Promotes Gentamicin Resistance
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Self-citationVibrational spectroscopy unveils distinct cell cycle features of cancer stem cells in melanoma
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Stimulated Raman Scattering Imaging Enabled Biomarker Discovery for Precision Medicine
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Mechanism of Cytotoxic Action of Gold Nanorods Photothermal Therapy for A549 Cell
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Raman Imaging Reveals Insights into Membrane Phase Biophysics in Cells
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- Authors
- Du, J., Su, Y., Qian, C., Yuan, D., Miao, K., Lee, D., Ng, A. H. C., Wijker, R. S., Ribas, A., Levine, R. D., Heath, J. R., & Wei, L.
- Affiliations
- California Institute of Technology (US)
- Institute for Systems Biology (US)
- University of California, Los Angeles (US)
- Corresponding author
- Heath, James R.
- Wei, Lu
- ORCID
- Venue
- Nature Communications
- Published
- 2020-09-24
- Volume
- 11
- Issue
- 1
- Pages
- 4830-4830
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC7518429
- OpenAlex
- W3087886129
- Cited by
- 171
- References
- 85
- Citations by year
- 2026: 18 · 2025: 34 · 2024: 32 · 2023: 44 · 2022: 28 · 2021: 14 · 2020: 1
- FWCI
- 10.35
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- CaltechAUTHORS (California Institute of Technology) (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- California Institute of Technology (start-up)
- U.S. Department of Health & Human Services | National Institutes of Health (U01 CA217655)
- The Parker Institute for Cancer Immunotherapy, the WA State Andy Hill CARE Foundation, and an ISB Innovator Award.
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Spectroscopy Techniques in Biomedical and Chemical Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Keywords
- metastatic melanoma, Raman spectroscopy, stimulated Raman scattering microscopy, single-cell metabolomics, fatty acid synthesis, lipid droplets, BRAF inhibitor resistance, dedifferentiation, lipidomics, transcriptomics, membrane phase separation, apoptosis
- MeSH terms
- Lipidomics, Fatty Acids, Humans, Lipids, Melanoma, Microscopy, Spectrum Analysis, Raman, Stearoyl-CoA Desaturase, Apoptosis, Oleic Acid, Cell Line, Tumor, Lipid Metabolism, Metabolomics, Transcriptome, Lipid Droplets
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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