Biophysical and biochemical signatures of pancreatic stellate cell activation: insights into mechano-metabolic signalling from atomic force microscopy and Raman spectroscopy
Abstract Background Pancreatic fibrosis is a key pathological feature of chronic pancreatitis and pancreatic cancer, driven by the persistent activation of pancreatic stellate cells. These cells, normally quiescent, undergo profound phenotypic changes in response to environmental cues, yet the inter...
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BMC
2025-08-01
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| Series: | Cell Communication and Signaling |
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| Online Access: | https://doi.org/10.1186/s12964-025-02354-1 |
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| author | Jacek J. Litewka Monika A. Jakubowska Marta Targosz-Korecka Ewelina Wiercigroch Jakub Dybas Natalia Cisak Zbigniew Madeja Pawel E. Ferdek |
| author_facet | Jacek J. Litewka Monika A. Jakubowska Marta Targosz-Korecka Ewelina Wiercigroch Jakub Dybas Natalia Cisak Zbigniew Madeja Pawel E. Ferdek |
| author_sort | Jacek J. Litewka |
| collection | DOAJ |
| description | Abstract Background Pancreatic fibrosis is a key pathological feature of chronic pancreatitis and pancreatic cancer, driven by the persistent activation of pancreatic stellate cells. These cells, normally quiescent, undergo profound phenotypic changes in response to environmental cues, yet the interplay between mechanical forces and metabolic reprogramming during this transition remains poorly understood. As the stromal microenvironment actively communicates with epithelial and vascular compartments, understanding this mechano-metabolic signalling axis is critical for uncovering novel mechanisms of tissue remodelling. Methods To investigate the biomechanical and biochemical alterations during stellate cell activation, we employed atomic force microscopy and Raman spectroscopy to measure changes in cell stiffness, morphology, and molecular composition. These data were complemented by transcriptomic analyses to evaluate gene expression profiles related to lipid metabolism and autophagy. Quantitative statistical tests, including ANOVA and Kruskal-Wallis tests with appropriate post hoc corrections, were applied. Results Activation of human pancreatic stellate cells led to progressive cytoskeletal remodelling, increased cellular stiffness, and a flattened morphology. Raman spectroscopy revealed an expansion of the cytoplasmic area, changes in nucleic acid signal, and significant increases in lipid content, particularly in unsaturated lipids and triacylglycerols. Gene expression analysis demonstrated upregulation of lipid elongation and desaturation pathways, along with enhanced autophagy, suggesting a coordinated metabolic adaptation. These changes support the myofibroblast-like phenotype and may influence intercellular signalling by altering extracellular matrix composition, mechanical tension, and the release of signalling molecules that affect the surrounding microenvironment. Conclusions Our findings reveal that pancreatic stellate cell activation involves a tightly coupled shift in mechanical and metabolic states, highlighting an integrated signalling process that may modulate stromal–vascular and stromal–epithelial communication. This mechano-metabolic axis represents a potential therapeutic target in fibrotic and neoplastic pancreatic diseases, where aberrant stromal signalling contributes to disease progression. |
| format | Article |
| id | doaj-art-1ce9fce95f2a45a79d0fb2aa0ff61af0 |
| institution | Kabale University |
| issn | 1478-811X |
| language | English |
| publishDate | 2025-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell Communication and Signaling |
| spelling | doaj-art-1ce9fce95f2a45a79d0fb2aa0ff61af02025-08-20T03:46:23ZengBMCCell Communication and Signaling1478-811X2025-08-0123112010.1186/s12964-025-02354-1Biophysical and biochemical signatures of pancreatic stellate cell activation: insights into mechano-metabolic signalling from atomic force microscopy and Raman spectroscopyJacek J. Litewka0Monika A. Jakubowska1Marta Targosz-Korecka2Ewelina Wiercigroch3Jakub Dybas4Natalia Cisak5Zbigniew Madeja6Pawel E. Ferdek7Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian UniversityMalopolska Centre of Biotechnology, Jagiellonian UniversityDepartment of Physics of Nanostructures and Nanotechnology, Faculty of Physics, Astronomy and Applied Computer Science, Jagiellonian UniversityJagiellonian Center of InnovationJagiellonian Center of InnovationDepartment of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian UniversityDepartment of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian UniversityDepartment of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian UniversityAbstract Background Pancreatic fibrosis is a key pathological feature of chronic pancreatitis and pancreatic cancer, driven by the persistent activation of pancreatic stellate cells. These cells, normally quiescent, undergo profound phenotypic changes in response to environmental cues, yet the interplay between mechanical forces and metabolic reprogramming during this transition remains poorly understood. As the stromal microenvironment actively communicates with epithelial and vascular compartments, understanding this mechano-metabolic signalling axis is critical for uncovering novel mechanisms of tissue remodelling. Methods To investigate the biomechanical and biochemical alterations during stellate cell activation, we employed atomic force microscopy and Raman spectroscopy to measure changes in cell stiffness, morphology, and molecular composition. These data were complemented by transcriptomic analyses to evaluate gene expression profiles related to lipid metabolism and autophagy. Quantitative statistical tests, including ANOVA and Kruskal-Wallis tests with appropriate post hoc corrections, were applied. Results Activation of human pancreatic stellate cells led to progressive cytoskeletal remodelling, increased cellular stiffness, and a flattened morphology. Raman spectroscopy revealed an expansion of the cytoplasmic area, changes in nucleic acid signal, and significant increases in lipid content, particularly in unsaturated lipids and triacylglycerols. Gene expression analysis demonstrated upregulation of lipid elongation and desaturation pathways, along with enhanced autophagy, suggesting a coordinated metabolic adaptation. These changes support the myofibroblast-like phenotype and may influence intercellular signalling by altering extracellular matrix composition, mechanical tension, and the release of signalling molecules that affect the surrounding microenvironment. Conclusions Our findings reveal that pancreatic stellate cell activation involves a tightly coupled shift in mechanical and metabolic states, highlighting an integrated signalling process that may modulate stromal–vascular and stromal–epithelial communication. This mechano-metabolic axis represents a potential therapeutic target in fibrotic and neoplastic pancreatic diseases, where aberrant stromal signalling contributes to disease progression.https://doi.org/10.1186/s12964-025-02354-1Pancreatic stellate cellsFibrosisLipid metabolismCytoskeletal remodellingMechanical propertiesRaman spectroscopy |
| spellingShingle | Jacek J. Litewka Monika A. Jakubowska Marta Targosz-Korecka Ewelina Wiercigroch Jakub Dybas Natalia Cisak Zbigniew Madeja Pawel E. Ferdek Biophysical and biochemical signatures of pancreatic stellate cell activation: insights into mechano-metabolic signalling from atomic force microscopy and Raman spectroscopy Cell Communication and Signaling Pancreatic stellate cells Fibrosis Lipid metabolism Cytoskeletal remodelling Mechanical properties Raman spectroscopy |
| title | Biophysical and biochemical signatures of pancreatic stellate cell activation: insights into mechano-metabolic signalling from atomic force microscopy and Raman spectroscopy |
| title_full | Biophysical and biochemical signatures of pancreatic stellate cell activation: insights into mechano-metabolic signalling from atomic force microscopy and Raman spectroscopy |
| title_fullStr | Biophysical and biochemical signatures of pancreatic stellate cell activation: insights into mechano-metabolic signalling from atomic force microscopy and Raman spectroscopy |
| title_full_unstemmed | Biophysical and biochemical signatures of pancreatic stellate cell activation: insights into mechano-metabolic signalling from atomic force microscopy and Raman spectroscopy |
| title_short | Biophysical and biochemical signatures of pancreatic stellate cell activation: insights into mechano-metabolic signalling from atomic force microscopy and Raman spectroscopy |
| title_sort | biophysical and biochemical signatures of pancreatic stellate cell activation insights into mechano metabolic signalling from atomic force microscopy and raman spectroscopy |
| topic | Pancreatic stellate cells Fibrosis Lipid metabolism Cytoskeletal remodelling Mechanical properties Raman spectroscopy |
| url | https://doi.org/10.1186/s12964-025-02354-1 |
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