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The nuclear piston activates mechanosensitive ion channels to generate cell migration paths in confining microenvironments
Cell migration in confining microenvironments is limited by the ability of the stiff nucleus to deform through pores when migration paths are preexisting and elastic, but how cells generate these paths remains unclear. Here, we reveal a mechanism by which the nucleus mechanically generates migration...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793582/ https://www.ncbi.nlm.nih.gov/pubmed/33523987 http://dx.doi.org/10.1126/sciadv.abd4058 |
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author | Lee, Hong-pyo Alisafaei, Farid Adebawale, Kolade Chang, Julie Shenoy, Vivek B. Chaudhuri, Ovijit |
author_facet | Lee, Hong-pyo Alisafaei, Farid Adebawale, Kolade Chang, Julie Shenoy, Vivek B. Chaudhuri, Ovijit |
author_sort | Lee, Hong-pyo |
collection | PubMed |
description | Cell migration in confining microenvironments is limited by the ability of the stiff nucleus to deform through pores when migration paths are preexisting and elastic, but how cells generate these paths remains unclear. Here, we reveal a mechanism by which the nucleus mechanically generates migration paths for mesenchymal stem cells (MSCs) in confining microenvironments. MSCs migrate robustly in nanoporous, confining hydrogels that are viscoelastic and plastic but not in hydrogels that are more elastic. To migrate, MSCs first extend thin protrusions that widen over time because of a nuclear piston, thus opening up a migration path in a confining matrix. Theoretical modeling and experiments indicate that the nucleus pushing into the protrusion activates mechanosensitive ion channels, leading to an influx of ions that increases osmotic pressure, which outcompetes hydrostatic pressure to drive protrusion expansion. Thus, instead of limiting migration, the nucleus powers migration by generating migration paths. |
format | Online Article Text |
id | pubmed-7793582 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-77935822021-01-15 The nuclear piston activates mechanosensitive ion channels to generate cell migration paths in confining microenvironments Lee, Hong-pyo Alisafaei, Farid Adebawale, Kolade Chang, Julie Shenoy, Vivek B. Chaudhuri, Ovijit Sci Adv Research Articles Cell migration in confining microenvironments is limited by the ability of the stiff nucleus to deform through pores when migration paths are preexisting and elastic, but how cells generate these paths remains unclear. Here, we reveal a mechanism by which the nucleus mechanically generates migration paths for mesenchymal stem cells (MSCs) in confining microenvironments. MSCs migrate robustly in nanoporous, confining hydrogels that are viscoelastic and plastic but not in hydrogels that are more elastic. To migrate, MSCs first extend thin protrusions that widen over time because of a nuclear piston, thus opening up a migration path in a confining matrix. Theoretical modeling and experiments indicate that the nucleus pushing into the protrusion activates mechanosensitive ion channels, leading to an influx of ions that increases osmotic pressure, which outcompetes hydrostatic pressure to drive protrusion expansion. Thus, instead of limiting migration, the nucleus powers migration by generating migration paths. American Association for the Advancement of Science 2021-01-08 /pmc/articles/PMC7793582/ /pubmed/33523987 http://dx.doi.org/10.1126/sciadv.abd4058 Text en Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). https://creativecommons.org/licenses/by-nc/4.0/ https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (https://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. |
spellingShingle | Research Articles Lee, Hong-pyo Alisafaei, Farid Adebawale, Kolade Chang, Julie Shenoy, Vivek B. Chaudhuri, Ovijit The nuclear piston activates mechanosensitive ion channels to generate cell migration paths in confining microenvironments |
title | The nuclear piston activates mechanosensitive ion channels to generate cell migration paths in confining microenvironments |
title_full | The nuclear piston activates mechanosensitive ion channels to generate cell migration paths in confining microenvironments |
title_fullStr | The nuclear piston activates mechanosensitive ion channels to generate cell migration paths in confining microenvironments |
title_full_unstemmed | The nuclear piston activates mechanosensitive ion channels to generate cell migration paths in confining microenvironments |
title_short | The nuclear piston activates mechanosensitive ion channels to generate cell migration paths in confining microenvironments |
title_sort | nuclear piston activates mechanosensitive ion channels to generate cell migration paths in confining microenvironments |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793582/ https://www.ncbi.nlm.nih.gov/pubmed/33523987 http://dx.doi.org/10.1126/sciadv.abd4058 |
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