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Published April 24, 2024 | Published
Journal Article Open

Seeing is Believing: Developing Multimodal Metabolic Insights at the Molecular Level

  • 1. ROR icon California Institute of Technology

Abstract

This outlook explores how two different molecular imaging approaches might be combined to gain insight into dynamic, subcellular metabolic processes. Specifically, we discuss how matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) and stimulated Raman scattering (SRS) microscopy, which have significantly pushed the boundaries of imaging metabolic and metabolomic analyses in their own right, could be combined to create comprehensive molecular images. We first briefly summarize the recent advances for each technique. We then explore how one might overcome the inherent limitations of each individual method, by envisioning orthogonal and interchangeable workflows. Additionally, we delve into the potential benefits of adopting a complementary approach that combines both MSI and SRS spectro-microscopy for informing on specific chemical structures through functional-group-specific targets. Ultimately, by integrating the strengths of both imaging modalities, researchers can achieve a more comprehensive understanding of biological and chemical systems, enabling precise metabolic investigations. This synergistic approach holds substantial promise to expand our toolkit for studying metabolites in complex environments.

Copyright and License

© 2024 The Authors. Published by American Chemical Society. This publication is licensed under CC-BY 4.0.

Acknowledgement

Funding from the National Institute of General Medical Sciences Award Number R21GM148870 (L.M.S.), the National Cancer Institute Award Number R01CA240423 of the National Institutes of Health, the National Science Foundation Grant IOS-2220510 (L.M.S.), and the Allen Distinguished Investigator Award (L.M.S.), a Paul G. Allen Frontiers Group advised grant of the Paul G. Allen Family Foundation is acknowledged. L.W. acknowledges support from an NIH Director’s New Innovator Award (DP2 GM140919-01), an Alfred P. Sloan Research Fellowship; a Shurl and Kay Curci Foundation grant; and a CZI Dynamic Imaging grant. L.W. is a Heritage Principal Investigator supported by the Heritage Medical Research Institute at Caltech.

Data Availability

  • List of metabolites for stimulated Raman imaging of untargeted (unlabeled) or targeted (labeled using biorthogonal tags) along with their Raman shift (cm–1) and vibrational contrast; list of acronyms and nonstandard abbreviations (PDF)

  • Transparent Peer Review report available (PDF)

Conflict of Interest

The authors declare no competing financial interest.

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Additional details

Created:
May 1, 2024
Modified:
May 1, 2024