Insights into metabolic changes during epidermal differentiation as revealed by multiphoton microscopy with fluorescence lifetime imaging

Abstract Rapid developments in the field of organotypic cultures have generated a growing need for effective and non-invasive methods for quality control during tissue development. In this study, we correlate metabolic changes with epidermal differentiation and demonstrate that multiphoton microscop...

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Main Authors: Monika Malak, Chen Qian, Jeemol James, Syam Nair, Julie Grantham, Marica B. Ericson
Format: Article
Language:English
Published: Nature Portfolio 2025-02-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-90101-4
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author Monika Malak
Chen Qian
Jeemol James
Syam Nair
Julie Grantham
Marica B. Ericson
author_facet Monika Malak
Chen Qian
Jeemol James
Syam Nair
Julie Grantham
Marica B. Ericson
author_sort Monika Malak
collection DOAJ
description Abstract Rapid developments in the field of organotypic cultures have generated a growing need for effective and non-invasive methods for quality control during tissue development. In this study, we correlate metabolic changes with epidermal differentiation and demonstrate that multiphoton microscopy with fluorescence lifetime imaging (MPM-FLIM) can be applied to monitor epidermal differentiation of keratinocytes with respect to proliferative and differentiated states. In a 2D keratinocyte tissue culture model, increased expression of differentiation markers keratin-1 and keratin-10 was induced with calcium supplementation. An accompanying shift from glycolysis to mitochondrial respiration was detected in metabolic flux assays. Analysis of MPM-FLIM images acquired at 750 nm and 900 nm excitation revealed a decreased relative fraction of intracellular NADH and FAD after high calcium treatment, consistent with increased oxidative phosphorylation. Epidermal differentiation could be monitored over a 96 h period. Discrimination analysis based on k-means clustering generated clusters that correlated well with the duration of high Ca2+ treatment, suggesting that MPM-FLIM can provide useful parameters for monitoring keratinocyte differentiation.
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spelling doaj-art-3c422905ca4e4d6794f35761cbb748ef2025-08-20T02:15:00ZengNature PortfolioScientific Reports2045-23222025-02-0115111310.1038/s41598-025-90101-4Insights into metabolic changes during epidermal differentiation as revealed by multiphoton microscopy with fluorescence lifetime imagingMonika Malak0Chen Qian1Jeemol James2Syam Nair3Julie Grantham4Marica B. Ericson5Department of Chemistry and Molecular Biology, Faculty of Science, University of GothenburgDepartment of Chemistry and Molecular Biology, Faculty of Science, University of GothenburgDepartment of Chemistry and Molecular Biology, Faculty of Science, University of GothenburgInstitute of Neuroscience and Physiology, The Sahlgrenska Academy, University of GothenburgDepartment of Chemistry and Molecular Biology, Faculty of Science, University of GothenburgDepartment of Chemistry and Molecular Biology, Faculty of Science, University of GothenburgAbstract Rapid developments in the field of organotypic cultures have generated a growing need for effective and non-invasive methods for quality control during tissue development. In this study, we correlate metabolic changes with epidermal differentiation and demonstrate that multiphoton microscopy with fluorescence lifetime imaging (MPM-FLIM) can be applied to monitor epidermal differentiation of keratinocytes with respect to proliferative and differentiated states. In a 2D keratinocyte tissue culture model, increased expression of differentiation markers keratin-1 and keratin-10 was induced with calcium supplementation. An accompanying shift from glycolysis to mitochondrial respiration was detected in metabolic flux assays. Analysis of MPM-FLIM images acquired at 750 nm and 900 nm excitation revealed a decreased relative fraction of intracellular NADH and FAD after high calcium treatment, consistent with increased oxidative phosphorylation. Epidermal differentiation could be monitored over a 96 h period. Discrimination analysis based on k-means clustering generated clusters that correlated well with the duration of high Ca2+ treatment, suggesting that MPM-FLIM can provide useful parameters for monitoring keratinocyte differentiation.https://doi.org/10.1038/s41598-025-90101-4Multiphoton microscopyFluorescence lifetime imagingEpidermal differentiationMetabolismLabel-free imaging
spellingShingle Monika Malak
Chen Qian
Jeemol James
Syam Nair
Julie Grantham
Marica B. Ericson
Insights into metabolic changes during epidermal differentiation as revealed by multiphoton microscopy with fluorescence lifetime imaging
Scientific Reports
Multiphoton microscopy
Fluorescence lifetime imaging
Epidermal differentiation
Metabolism
Label-free imaging
title Insights into metabolic changes during epidermal differentiation as revealed by multiphoton microscopy with fluorescence lifetime imaging
title_full Insights into metabolic changes during epidermal differentiation as revealed by multiphoton microscopy with fluorescence lifetime imaging
title_fullStr Insights into metabolic changes during epidermal differentiation as revealed by multiphoton microscopy with fluorescence lifetime imaging
title_full_unstemmed Insights into metabolic changes during epidermal differentiation as revealed by multiphoton microscopy with fluorescence lifetime imaging
title_short Insights into metabolic changes during epidermal differentiation as revealed by multiphoton microscopy with fluorescence lifetime imaging
title_sort insights into metabolic changes during epidermal differentiation as revealed by multiphoton microscopy with fluorescence lifetime imaging
topic Multiphoton microscopy
Fluorescence lifetime imaging
Epidermal differentiation
Metabolism
Label-free imaging
url https://doi.org/10.1038/s41598-025-90101-4
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