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Multiparametric physicochemical analysis of a type 1 collagen 3D cell culture model using light and electron microscopy and mass spectrometry imaging

Dondi, Camilla; Tsikritsis, Dimitrios; Vorng, Jean-Luc; Greenidge, Gina; Kepiro, Ibolya E; Belsey, Natalie A; McMahon, Greg; ... Shaw, Michael; + view all (2025) Multiparametric physicochemical analysis of a type 1 collagen 3D cell culture model using light and electron microscopy and mass spectrometry imaging. Scientific Reports , 15 , Article 9578. 10.1038/s41598-025-93700-3. Green open access

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Abstract

Three-dimensional cell culture systems underpin cell-based technologies ranging from tissue scaffolds for regenerative medicine to tumor models and organoids for drug screening. However, to realise the full potential of these technologies requires analytical methods able to capture the diverse information needed to characterize constituent cells, scaffold components and the extracellular milieu. Here we describe a multimodal imaging workflow which combines fluorescence, vibrational and second harmonic generation microscopy with secondary ion mass spectrometry imaging and transmission electron microscopy to analyse the morphological, chemical and ultrastructural properties of cell-seeded scaffolds. Using cell nuclei as landmarks we register fluorescence with label-free optical microscopy images and high mass resolution with high spatial resolution secondary ion mass spectrometry images, with an accuracy comparable to the intrinsic spatial resolution of the techniques. We apply these methods to investigate relationships between cell distribution, cytoskeletal morphology, scaffold fiber organisation and biomolecular composition in type I collagen scaffolds seeded with human dermal fibroblasts.

Type: Article
Title: Multiparametric physicochemical analysis of a type 1 collagen 3D cell culture model using light and electron microscopy and mass spectrometry imaging
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41598-025-93700-3
Publisher version: https://doi.org/10.1038/s41598-025-93700-3
Language: English
Additional information: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
Keywords: Cellular imaging; Cytoskeleton; Imaging; Mass spectrometry; Microscopy; Optical imaging; Optical spectroscopy
UCL classification: UCL
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Computer Science
URI: https://discovery.ucl.ac.uk/id/eprint/10206827
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