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The desmoplakin–intermediate filament linkage regulates cell mechanics

The translation of mechanical forces into biochemical signals plays a central role in guiding normal physiological processes during tissue development and homeostasis. Interfering with this process contributes to cardiovascular disease, cancer progression, and inherited disorders. The actin-based cy...

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Autores principales: Broussard, Joshua A., Yang, Ruiguo, Huang, Changjin, Nathamgari, S. Shiva P., Beese, Allison M., Godsel, Lisa M., Hegazy, Marihan H., Lee, Sherry, Zhou, Fan, Sniadecki, Nathan J., Green, Kathleen J., Espinosa, Horacio D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5687018/
https://www.ncbi.nlm.nih.gov/pubmed/28495795
http://dx.doi.org/10.1091/mbc.E16-07-0520
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author Broussard, Joshua A.
Yang, Ruiguo
Huang, Changjin
Nathamgari, S. Shiva P.
Beese, Allison M.
Godsel, Lisa M.
Hegazy, Marihan H.
Lee, Sherry
Zhou, Fan
Sniadecki, Nathan J.
Green, Kathleen J.
Espinosa, Horacio D.
author_facet Broussard, Joshua A.
Yang, Ruiguo
Huang, Changjin
Nathamgari, S. Shiva P.
Beese, Allison M.
Godsel, Lisa M.
Hegazy, Marihan H.
Lee, Sherry
Zhou, Fan
Sniadecki, Nathan J.
Green, Kathleen J.
Espinosa, Horacio D.
author_sort Broussard, Joshua A.
collection PubMed
description The translation of mechanical forces into biochemical signals plays a central role in guiding normal physiological processes during tissue development and homeostasis. Interfering with this process contributes to cardiovascular disease, cancer progression, and inherited disorders. The actin-based cytoskeleton and its associated adherens junctions are well-established contributors to mechanosensing and transduction machinery; however, the role of the desmosome–intermediate filament (DSM–IF) network is poorly understood in this context. Because a force balance among different cytoskeletal systems is important to maintain normal tissue function, knowing the relative contributions of these structurally integrated systems to cell mechanics is critical. Here we modulated the interaction between DSMs and IFs using mutant forms of desmoplakin, the protein bridging these structures. Using micropillar arrays and atomic force microscopy, we demonstrate that strengthening the DSM–IF interaction increases cell–substrate and cell–cell forces and cell stiffness both in cell pairs and sheets of cells. In contrast, disrupting the interaction leads to a decrease in these forces. These alterations in cell mechanics are abrogated when the actin cytoskeleton is dismantled. These data suggest that the tissue-specific variability in DSM–IF network composition provides an opportunity to differentially regulate tissue mechanics by balancing and tuning forces among cytoskeletal systems.
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spelling pubmed-56870182018-01-22 The desmoplakin–intermediate filament linkage regulates cell mechanics Broussard, Joshua A. Yang, Ruiguo Huang, Changjin Nathamgari, S. Shiva P. Beese, Allison M. Godsel, Lisa M. Hegazy, Marihan H. Lee, Sherry Zhou, Fan Sniadecki, Nathan J. Green, Kathleen J. Espinosa, Horacio D. Mol Biol Cell Brief Reports The translation of mechanical forces into biochemical signals plays a central role in guiding normal physiological processes during tissue development and homeostasis. Interfering with this process contributes to cardiovascular disease, cancer progression, and inherited disorders. The actin-based cytoskeleton and its associated adherens junctions are well-established contributors to mechanosensing and transduction machinery; however, the role of the desmosome–intermediate filament (DSM–IF) network is poorly understood in this context. Because a force balance among different cytoskeletal systems is important to maintain normal tissue function, knowing the relative contributions of these structurally integrated systems to cell mechanics is critical. Here we modulated the interaction between DSMs and IFs using mutant forms of desmoplakin, the protein bridging these structures. Using micropillar arrays and atomic force microscopy, we demonstrate that strengthening the DSM–IF interaction increases cell–substrate and cell–cell forces and cell stiffness both in cell pairs and sheets of cells. In contrast, disrupting the interaction leads to a decrease in these forces. These alterations in cell mechanics are abrogated when the actin cytoskeleton is dismantled. These data suggest that the tissue-specific variability in DSM–IF network composition provides an opportunity to differentially regulate tissue mechanics by balancing and tuning forces among cytoskeletal systems. The American Society for Cell Biology 2017-11-07 /pmc/articles/PMC5687018/ /pubmed/28495795 http://dx.doi.org/10.1091/mbc.E16-07-0520 Text en © 2017 Broussard, Yang, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology.
spellingShingle Brief Reports
Broussard, Joshua A.
Yang, Ruiguo
Huang, Changjin
Nathamgari, S. Shiva P.
Beese, Allison M.
Godsel, Lisa M.
Hegazy, Marihan H.
Lee, Sherry
Zhou, Fan
Sniadecki, Nathan J.
Green, Kathleen J.
Espinosa, Horacio D.
The desmoplakin–intermediate filament linkage regulates cell mechanics
title The desmoplakin–intermediate filament linkage regulates cell mechanics
title_full The desmoplakin–intermediate filament linkage regulates cell mechanics
title_fullStr The desmoplakin–intermediate filament linkage regulates cell mechanics
title_full_unstemmed The desmoplakin–intermediate filament linkage regulates cell mechanics
title_short The desmoplakin–intermediate filament linkage regulates cell mechanics
title_sort desmoplakin–intermediate filament linkage regulates cell mechanics
topic Brief Reports
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5687018/
https://www.ncbi.nlm.nih.gov/pubmed/28495795
http://dx.doi.org/10.1091/mbc.E16-07-0520
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