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Physicochemical mechanotransduction alters nuclear shape and mechanics via heterochromatin formation
The nucleus houses, organizes, and protects chromatin to ensure genome integrity and proper gene expression, but how the nucleus adapts mechanically to changes in the extracellular environment is poorly understood. Recent studies have revealed that extracellular physical stresses induce chromatin co...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6743459/ https://www.ncbi.nlm.nih.gov/pubmed/31365328 http://dx.doi.org/10.1091/mbc.E19-05-0286 |
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author | Stephens, Andrew D. Liu, Patrick Z. Kandula, Viswajit Chen, Haimei Almassalha, Luay M. Herman, Cameron Backman, Vadim O’Halloran, Thomas Adam, Stephen A. Goldman, Robert D. Banigan, Edward J. Marko, John F. |
author_facet | Stephens, Andrew D. Liu, Patrick Z. Kandula, Viswajit Chen, Haimei Almassalha, Luay M. Herman, Cameron Backman, Vadim O’Halloran, Thomas Adam, Stephen A. Goldman, Robert D. Banigan, Edward J. Marko, John F. |
author_sort | Stephens, Andrew D. |
collection | PubMed |
description | The nucleus houses, organizes, and protects chromatin to ensure genome integrity and proper gene expression, but how the nucleus adapts mechanically to changes in the extracellular environment is poorly understood. Recent studies have revealed that extracellular physical stresses induce chromatin compaction via mechanotransductive processes. We report that increased extracellular multivalent cations lead to increased heterochromatin levels through activation of mechanosensitive ion channels (MSCs), without large-scale cell stretching. In cells with perturbed chromatin or lamins, this increase in heterochromatin suppresses nuclear blebbing associated with nuclear rupture and DNA damage. Through micromanipulation force measurements, we show that this increase in heterochromatin increases chromatin-based nuclear rigidity, which protects nuclear morphology and function. In addition, transduction of elevated extracellular cations rescues nuclear morphology in model and patient cells of human diseases, including progeria and the breast cancer model cell line MDA-MB-231. We conclude that nuclear mechanics, morphology, and function can be modulated by cell sensing of the extracellular environment through MSCs and consequent changes to histone modification state and chromatin-based nuclear rigidity. |
format | Online Article Text |
id | pubmed-6743459 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-67434592019-10-16 Physicochemical mechanotransduction alters nuclear shape and mechanics via heterochromatin formation Stephens, Andrew D. Liu, Patrick Z. Kandula, Viswajit Chen, Haimei Almassalha, Luay M. Herman, Cameron Backman, Vadim O’Halloran, Thomas Adam, Stephen A. Goldman, Robert D. Banigan, Edward J. Marko, John F. Mol Biol Cell Articles The nucleus houses, organizes, and protects chromatin to ensure genome integrity and proper gene expression, but how the nucleus adapts mechanically to changes in the extracellular environment is poorly understood. Recent studies have revealed that extracellular physical stresses induce chromatin compaction via mechanotransductive processes. We report that increased extracellular multivalent cations lead to increased heterochromatin levels through activation of mechanosensitive ion channels (MSCs), without large-scale cell stretching. In cells with perturbed chromatin or lamins, this increase in heterochromatin suppresses nuclear blebbing associated with nuclear rupture and DNA damage. Through micromanipulation force measurements, we show that this increase in heterochromatin increases chromatin-based nuclear rigidity, which protects nuclear morphology and function. In addition, transduction of elevated extracellular cations rescues nuclear morphology in model and patient cells of human diseases, including progeria and the breast cancer model cell line MDA-MB-231. We conclude that nuclear mechanics, morphology, and function can be modulated by cell sensing of the extracellular environment through MSCs and consequent changes to histone modification state and chromatin-based nuclear rigidity. The American Society for Cell Biology 2019-08-01 /pmc/articles/PMC6743459/ /pubmed/31365328 http://dx.doi.org/10.1091/mbc.E19-05-0286 Text en © 2019 Stephens, Liu, et al. “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. http://creativecommons.org/licenses/by-nc-sa/3.0 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. |
spellingShingle | Articles Stephens, Andrew D. Liu, Patrick Z. Kandula, Viswajit Chen, Haimei Almassalha, Luay M. Herman, Cameron Backman, Vadim O’Halloran, Thomas Adam, Stephen A. Goldman, Robert D. Banigan, Edward J. Marko, John F. Physicochemical mechanotransduction alters nuclear shape and mechanics via heterochromatin formation |
title | Physicochemical mechanotransduction alters nuclear shape and mechanics via heterochromatin formation |
title_full | Physicochemical mechanotransduction alters nuclear shape and mechanics via heterochromatin formation |
title_fullStr | Physicochemical mechanotransduction alters nuclear shape and mechanics via heterochromatin formation |
title_full_unstemmed | Physicochemical mechanotransduction alters nuclear shape and mechanics via heterochromatin formation |
title_short | Physicochemical mechanotransduction alters nuclear shape and mechanics via heterochromatin formation |
title_sort | physicochemical mechanotransduction alters nuclear shape and mechanics via heterochromatin formation |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6743459/ https://www.ncbi.nlm.nih.gov/pubmed/31365328 http://dx.doi.org/10.1091/mbc.E19-05-0286 |
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