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Distinct ECM mechanosensing pathways regulate microtubule dynamics to control endothelial cell branching morphogenesis

During angiogenesis, cytoskeletal dynamics that mediate endothelial cell branching morphogenesis during vascular guidance are thought to be regulated by physical attributes of the extracellular matrix (ECM) in a process termed mechanosensing. Here, we tested the involvement of microtubules in linkin...

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Autores principales: Myers, Kenneth A., Applegate, Kathryn T., Danuser, Gaudenz, Fischer, Robert S., Waterman, Clare M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3172168/
https://www.ncbi.nlm.nih.gov/pubmed/21263030
http://dx.doi.org/10.1083/jcb.201006009
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author Myers, Kenneth A.
Applegate, Kathryn T.
Danuser, Gaudenz
Fischer, Robert S.
Waterman, Clare M.
author_facet Myers, Kenneth A.
Applegate, Kathryn T.
Danuser, Gaudenz
Fischer, Robert S.
Waterman, Clare M.
author_sort Myers, Kenneth A.
collection PubMed
description During angiogenesis, cytoskeletal dynamics that mediate endothelial cell branching morphogenesis during vascular guidance are thought to be regulated by physical attributes of the extracellular matrix (ECM) in a process termed mechanosensing. Here, we tested the involvement of microtubules in linking mechanosensing to endothelial cell branching morphogenesis. We used a recently developed microtubule plus end–tracking program to show that specific parameters of microtubule assembly dynamics, growth speed and growth persistence, are globally and regionally modified by, and contribute to, ECM mechanosensing. We demonstrated that engagement of compliant two-dimensional or three-dimensional ECMs induces local differences in microtubule growth speed that require myosin II contractility. Finally, we found that microtubule growth persistence is modulated by myosin II–mediated compliance mechanosensing when cells are cultured on two-dimensional ECMs, whereas three-dimensional ECM engagement makes microtubule growth persistence insensitive to changes in ECM compliance. Thus, compliance and dimensionality ECM mechanosensing pathways independently regulate specific and distinct microtubule dynamics parameters in endothelial cells to guide branching morphogenesis in physically complex ECMs.
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spelling pubmed-31721682011-09-14 Distinct ECM mechanosensing pathways regulate microtubule dynamics to control endothelial cell branching morphogenesis Myers, Kenneth A. Applegate, Kathryn T. Danuser, Gaudenz Fischer, Robert S. Waterman, Clare M. J Cell Biol Research Articles During angiogenesis, cytoskeletal dynamics that mediate endothelial cell branching morphogenesis during vascular guidance are thought to be regulated by physical attributes of the extracellular matrix (ECM) in a process termed mechanosensing. Here, we tested the involvement of microtubules in linking mechanosensing to endothelial cell branching morphogenesis. We used a recently developed microtubule plus end–tracking program to show that specific parameters of microtubule assembly dynamics, growth speed and growth persistence, are globally and regionally modified by, and contribute to, ECM mechanosensing. We demonstrated that engagement of compliant two-dimensional or three-dimensional ECMs induces local differences in microtubule growth speed that require myosin II contractility. Finally, we found that microtubule growth persistence is modulated by myosin II–mediated compliance mechanosensing when cells are cultured on two-dimensional ECMs, whereas three-dimensional ECM engagement makes microtubule growth persistence insensitive to changes in ECM compliance. Thus, compliance and dimensionality ECM mechanosensing pathways independently regulate specific and distinct microtubule dynamics parameters in endothelial cells to guide branching morphogenesis in physically complex ECMs. The Rockefeller University Press 2011-01-24 /pmc/articles/PMC3172168/ /pubmed/21263030 http://dx.doi.org/10.1083/jcb.201006009 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Research Articles
Myers, Kenneth A.
Applegate, Kathryn T.
Danuser, Gaudenz
Fischer, Robert S.
Waterman, Clare M.
Distinct ECM mechanosensing pathways regulate microtubule dynamics to control endothelial cell branching morphogenesis
title Distinct ECM mechanosensing pathways regulate microtubule dynamics to control endothelial cell branching morphogenesis
title_full Distinct ECM mechanosensing pathways regulate microtubule dynamics to control endothelial cell branching morphogenesis
title_fullStr Distinct ECM mechanosensing pathways regulate microtubule dynamics to control endothelial cell branching morphogenesis
title_full_unstemmed Distinct ECM mechanosensing pathways regulate microtubule dynamics to control endothelial cell branching morphogenesis
title_short Distinct ECM mechanosensing pathways regulate microtubule dynamics to control endothelial cell branching morphogenesis
title_sort distinct ecm mechanosensing pathways regulate microtubule dynamics to control endothelial cell branching morphogenesis
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3172168/
https://www.ncbi.nlm.nih.gov/pubmed/21263030
http://dx.doi.org/10.1083/jcb.201006009
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