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MeXpose-A Modular Imaging Pipeline for the Quantitative Assessment of Cellular Metal Bioaccumulation
Gabriel Braun1,2, Martin Schaier1,2, Paulina Werner3
1Institute of Analytical Chemistry, Faculty of Chemistry, University of Vienna, 1090 Vienna, Austria.
JACS Au
|June 28, 2024
Summary
MeXpose, a new pipeline, reveals how metals like cobalt accumulate in single cells, linking metal exposure to DNA damage in human skin. This advances toxicological and therapeutic research.
Area of Science:
- Biomedical Imaging
- Toxicology
- Metallomics
Background:
- Understanding metal bioaccumulation at the cellular level is crucial for toxicology.
- Current methods lack the resolution to link metal exposure to specific cellular responses.
Purpose of the Study:
- To introduce MeXpose, an end-to-end pipeline for spatial single-cell metallomics.
- To quantify metal bioaccumulation and cellular responses in phenotypically characterized tissue.
Main Methods:
- Utilizes laser ablation-inductively coupled plasma time-of-flight mass spectrometry (LA-ICP-TOFMS) for high-resolution imaging.
- Integrates quantitative bioimaging with immunohistochemistry for cellular phenotyping.
- Analyzes metal isotopes from m/z 14-256 for comprehensive metallomics.
Main Results:
- Demonstrated high cobalt accumulation in the epidermis of an ex vivo human skin model, particularly in basal cells.
- Observed a correlation between cobalt accumulation and DNA damage in mitotic basal cells.
- Detected significant cobalt deposits in vascular cells and lower levels in dermal fibers.
Conclusions:
- MeXpose enables unprecedented insights into metal bioaccumulation at the single-cell level.
- The pipeline facilitates exploration of relationships between metal exposure and cellular responses.
- This approach is vital for advancing toxicological and therapeutic studies.
