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Data driven and biophysical insights into the regulation of trafficking vesicles by extracellular matrix stiffness
Biomechanical signals from remodeled extracellular matrix (ECM) promote tumor progression. Here, we show that cell-matrix and cell-cell communication may be inherently linked and tuned through mechanisms of mechanosensitive biogenesis of trafficking vesicles. Pan-cancer analysis of cancer cells'...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9293776/ https://www.ncbi.nlm.nih.gov/pubmed/35865140 http://dx.doi.org/10.1016/j.isci.2022.104721 |
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author | Parihar, Kshitiz Nukpezah, Jonathan Iwamoto, Daniel V. Janmey, Paul A. Radhakrishnan, Ravi |
author_facet | Parihar, Kshitiz Nukpezah, Jonathan Iwamoto, Daniel V. Janmey, Paul A. Radhakrishnan, Ravi |
author_sort | Parihar, Kshitiz |
collection | PubMed |
description | Biomechanical signals from remodeled extracellular matrix (ECM) promote tumor progression. Here, we show that cell-matrix and cell-cell communication may be inherently linked and tuned through mechanisms of mechanosensitive biogenesis of trafficking vesicles. Pan-cancer analysis of cancer cells' mechanical properties (focusing primarily on cell stiffness) on substrates of varied stiffness and composition elucidated a heterogeneous cellular response to mechanical stimuli. Through machine learning, we identified a fingerprint of cytoskeleton-related proteins that accurately characterize cell stiffness in different ECM conditions. Expression of their respective genes correlates with patient prognosis across different tumor types. The levels of selected cytoskeleton proteins indicated that cortical tension mirrors the increase (or decrease) in cell stiffness with a change in ECM stiffness. A mechanistic biophysical model shows that the tendency for curvature generation by curvature-inducing proteins has an ultrasensitive dependence on cortical tension. This study thus highlights the effect of ECM stiffness, mediated by cortical tension, in modulating vesicle biogenesis. |
format | Online Article Text |
id | pubmed-9293776 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-92937762022-07-20 Data driven and biophysical insights into the regulation of trafficking vesicles by extracellular matrix stiffness Parihar, Kshitiz Nukpezah, Jonathan Iwamoto, Daniel V. Janmey, Paul A. Radhakrishnan, Ravi iScience Article Biomechanical signals from remodeled extracellular matrix (ECM) promote tumor progression. Here, we show that cell-matrix and cell-cell communication may be inherently linked and tuned through mechanisms of mechanosensitive biogenesis of trafficking vesicles. Pan-cancer analysis of cancer cells' mechanical properties (focusing primarily on cell stiffness) on substrates of varied stiffness and composition elucidated a heterogeneous cellular response to mechanical stimuli. Through machine learning, we identified a fingerprint of cytoskeleton-related proteins that accurately characterize cell stiffness in different ECM conditions. Expression of their respective genes correlates with patient prognosis across different tumor types. The levels of selected cytoskeleton proteins indicated that cortical tension mirrors the increase (or decrease) in cell stiffness with a change in ECM stiffness. A mechanistic biophysical model shows that the tendency for curvature generation by curvature-inducing proteins has an ultrasensitive dependence on cortical tension. This study thus highlights the effect of ECM stiffness, mediated by cortical tension, in modulating vesicle biogenesis. Elsevier 2022-07-04 /pmc/articles/PMC9293776/ /pubmed/35865140 http://dx.doi.org/10.1016/j.isci.2022.104721 Text en © 2022 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Parihar, Kshitiz Nukpezah, Jonathan Iwamoto, Daniel V. Janmey, Paul A. Radhakrishnan, Ravi Data driven and biophysical insights into the regulation of trafficking vesicles by extracellular matrix stiffness |
title | Data driven and biophysical insights into the regulation of trafficking vesicles by extracellular matrix stiffness |
title_full | Data driven and biophysical insights into the regulation of trafficking vesicles by extracellular matrix stiffness |
title_fullStr | Data driven and biophysical insights into the regulation of trafficking vesicles by extracellular matrix stiffness |
title_full_unstemmed | Data driven and biophysical insights into the regulation of trafficking vesicles by extracellular matrix stiffness |
title_short | Data driven and biophysical insights into the regulation of trafficking vesicles by extracellular matrix stiffness |
title_sort | data driven and biophysical insights into the regulation of trafficking vesicles by extracellular matrix stiffness |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9293776/ https://www.ncbi.nlm.nih.gov/pubmed/35865140 http://dx.doi.org/10.1016/j.isci.2022.104721 |
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