3D-Mass Spectrometry Imaging of Micro-scale 3D Cell Culture Models in Cancer Research

Iakab, S. A.; Keller, F.; Schmidt, S.; Cordes, J.; Zhou, Q.; Cairns, J. J.; Fischer, F.; Schneider, R.; Wolf, I.; Rudolf, R.; Hopf, C.

doi:10.1101/2022.12.05.519157

bioRxiv · 10.1101/2022.12.05.519157

3D-Mass Spectrometry Imaging of Micro-scale 3D Cell Culture Models in Cancer Research

Iakab, S. A.·Keller, F.·Schmidt, S.·Cordes, J.·Zhou, Q.·Cairns, J. J.·Fischer, F.·Schneider, R.·Wolf, I.·Rudolf, R.·Hopf, C.

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Abstract

Three-dimensional (3D) human cell culture models have emerged as a key technology for personalized medicine and for phenotypic compound screening in more disease-like in-vitro systems. Mass spectrometry imaging (MSI) is one of the most versatile label-free techniques that enables simultaneous generation of spatial maps for multiple relevant molecules in these 3D-models. Here, we present an integrated platform for 3D-MSI of 3D-cell cultures comprising 3D-printed metal casting molds for freezing and embedding, MS imaging of 100 serial cryosections and their computational elastic 3D-reconstruction. With this platform, we monitored multiple lipids that were selectively associated with different cell-types or cell-cell interactions within 300 m-scale fibroblast and colon cancer biculture spheroids. Our findings suggest that 3D-printing-aided precise preparation of serial sections from small spheroids and visualization of marker molecules in 3D can provide a detailed overview of the cellular metabolic interplay in 3D cell culture models in cancer research and drug discovery.

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Iakab, S. A., Keller, F., Schmidt, S., Cordes, J., Zhou, Q., Cairns, J. J., Fischer, F., Schneider, R., Wolf, I., Rudolf, R., Hopf, C.. 2022-12-08. 3D-Mass Spectrometry Imaging of Micro-scale 3D Cell Culture Models in Cancer Research. https://doi.org/10.1101/2022.12.05.519157

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