Local 3D matrix microenvironment regulates cell migration through spatiotemporal dynamics of contractility-dependent adhesions

The physical properties of two-dimensional (2D) extracellular matrices (ECMs) modulate cell adhesion dynamics and motility, but little is known about the roles of local microenvironmental differences in three-dimensional (3D) ECMs. Here we generate 3D collagen gels of varying matrix microarchitectur...

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Autores principales: Doyle, Andrew D., Carvajal, Nicole, Jin, Albert, Matsumoto, Kazue, Yamada, Kenneth M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Pub. Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4643399/
https://www.ncbi.nlm.nih.gov/pubmed/26548801
http://dx.doi.org/10.1038/ncomms9720
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author Doyle, Andrew D.
Carvajal, Nicole
Jin, Albert
Matsumoto, Kazue
Yamada, Kenneth M.
author_facet Doyle, Andrew D.
Carvajal, Nicole
Jin, Albert
Matsumoto, Kazue
Yamada, Kenneth M.
author_sort Doyle, Andrew D.
collection PubMed
description The physical properties of two-dimensional (2D) extracellular matrices (ECMs) modulate cell adhesion dynamics and motility, but little is known about the roles of local microenvironmental differences in three-dimensional (3D) ECMs. Here we generate 3D collagen gels of varying matrix microarchitectures to characterize their regulation of 3D adhesion dynamics and cell migration. ECMs containing bundled fibrils demonstrate enhanced local adhesion-scale stiffness and increased adhesion stability through balanced ECM/adhesion coupling, whereas highly pliable reticular matrices promote adhesion retraction. 3D adhesion dynamics are locally regulated by ECM rigidity together with integrin/ECM association and myosin II contractility. Unlike 2D migration, abrogating contractility stalls 3D migration regardless of ECM pore size. We find force is not required for clustering of activated integrins on 3D native collagen fibrils. We propose that efficient 3D migration requires local balancing of contractility with ECM stiffness to stabilize adhesions, which facilitates the detachment of activated integrins from ECM fibrils.
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spelling pubmed-46433992015-12-10 Local 3D matrix microenvironment regulates cell migration through spatiotemporal dynamics of contractility-dependent adhesions Doyle, Andrew D. Carvajal, Nicole Jin, Albert Matsumoto, Kazue Yamada, Kenneth M. Nat Commun Article The physical properties of two-dimensional (2D) extracellular matrices (ECMs) modulate cell adhesion dynamics and motility, but little is known about the roles of local microenvironmental differences in three-dimensional (3D) ECMs. Here we generate 3D collagen gels of varying matrix microarchitectures to characterize their regulation of 3D adhesion dynamics and cell migration. ECMs containing bundled fibrils demonstrate enhanced local adhesion-scale stiffness and increased adhesion stability through balanced ECM/adhesion coupling, whereas highly pliable reticular matrices promote adhesion retraction. 3D adhesion dynamics are locally regulated by ECM rigidity together with integrin/ECM association and myosin II contractility. Unlike 2D migration, abrogating contractility stalls 3D migration regardless of ECM pore size. We find force is not required for clustering of activated integrins on 3D native collagen fibrils. We propose that efficient 3D migration requires local balancing of contractility with ECM stiffness to stabilize adhesions, which facilitates the detachment of activated integrins from ECM fibrils. Nature Pub. Group 2015-11-09 /pmc/articles/PMC4643399/ /pubmed/26548801 http://dx.doi.org/10.1038/ncomms9720 Text en Copyright © 2015, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Doyle, Andrew D.
Carvajal, Nicole
Jin, Albert
Matsumoto, Kazue
Yamada, Kenneth M.
Local 3D matrix microenvironment regulates cell migration through spatiotemporal dynamics of contractility-dependent adhesions
title Local 3D matrix microenvironment regulates cell migration through spatiotemporal dynamics of contractility-dependent adhesions
title_full Local 3D matrix microenvironment regulates cell migration through spatiotemporal dynamics of contractility-dependent adhesions
title_fullStr Local 3D matrix microenvironment regulates cell migration through spatiotemporal dynamics of contractility-dependent adhesions
title_full_unstemmed Local 3D matrix microenvironment regulates cell migration through spatiotemporal dynamics of contractility-dependent adhesions
title_short Local 3D matrix microenvironment regulates cell migration through spatiotemporal dynamics of contractility-dependent adhesions
title_sort local 3d matrix microenvironment regulates cell migration through spatiotemporal dynamics of contractility-dependent adhesions
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4643399/
https://www.ncbi.nlm.nih.gov/pubmed/26548801
http://dx.doi.org/10.1038/ncomms9720
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