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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'...

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Autores principales: Parihar, Kshitiz, Nukpezah, Jonathan, Iwamoto, Daniel V., Janmey, Paul A., Radhakrishnan, Ravi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
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.
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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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