Computational model of integrin adhesion elongation under an actin fiber

Cells create physical connections with the extracellular environment through adhesions. Nascent adhesions form at the leading edge of migrating cells and either undergo cycles of disassembly and reassembly, or elongate and stabilize at the end of actin fibers. How adhesions assemble has been address...

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Autores principales: Campbell, Samuel, Mendoza, Michelle C., Rammohan, Aravind, McKenzie, Matthew E., Bidone, Tamara C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10325090/
https://www.ncbi.nlm.nih.gov/pubmed/37410718
http://dx.doi.org/10.1371/journal.pcbi.1011237
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author Campbell, Samuel
Mendoza, Michelle C.
Rammohan, Aravind
McKenzie, Matthew E.
Bidone, Tamara C.
author_facet Campbell, Samuel
Mendoza, Michelle C.
Rammohan, Aravind
McKenzie, Matthew E.
Bidone, Tamara C.
author_sort Campbell, Samuel
collection PubMed
description Cells create physical connections with the extracellular environment through adhesions. Nascent adhesions form at the leading edge of migrating cells and either undergo cycles of disassembly and reassembly, or elongate and stabilize at the end of actin fibers. How adhesions assemble has been addressed in several studies, but the exact role of actin fibers in the elongation and stabilization of nascent adhesions remains largely elusive. To address this question, here we extended our computational model of adhesion assembly by incorporating an actin fiber that locally promotes integrin activation. The model revealed that an actin fiber promotes adhesion stabilization and elongation. Actomyosin contractility from the fiber also promotes adhesion stabilization and elongation, by strengthening integrin-ligand interactions, but only up to a force threshold. Above this force threshold, most integrin-ligand bonds fail, and the adhesion disassembles. In the absence of contraction, actin fibers still support adhesions stabilization. Collectively, our results provide a picture in which myosin activity is dispensable for adhesion stabilization and elongation under an actin fiber, offering a framework for interpreting several previous experimental observations.
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spelling pubmed-103250902023-07-07 Computational model of integrin adhesion elongation under an actin fiber Campbell, Samuel Mendoza, Michelle C. Rammohan, Aravind McKenzie, Matthew E. Bidone, Tamara C. PLoS Comput Biol Research Article Cells create physical connections with the extracellular environment through adhesions. Nascent adhesions form at the leading edge of migrating cells and either undergo cycles of disassembly and reassembly, or elongate and stabilize at the end of actin fibers. How adhesions assemble has been addressed in several studies, but the exact role of actin fibers in the elongation and stabilization of nascent adhesions remains largely elusive. To address this question, here we extended our computational model of adhesion assembly by incorporating an actin fiber that locally promotes integrin activation. The model revealed that an actin fiber promotes adhesion stabilization and elongation. Actomyosin contractility from the fiber also promotes adhesion stabilization and elongation, by strengthening integrin-ligand interactions, but only up to a force threshold. Above this force threshold, most integrin-ligand bonds fail, and the adhesion disassembles. In the absence of contraction, actin fibers still support adhesions stabilization. Collectively, our results provide a picture in which myosin activity is dispensable for adhesion stabilization and elongation under an actin fiber, offering a framework for interpreting several previous experimental observations. Public Library of Science 2023-07-06 /pmc/articles/PMC10325090/ /pubmed/37410718 http://dx.doi.org/10.1371/journal.pcbi.1011237 Text en © 2023 Campbell et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Campbell, Samuel
Mendoza, Michelle C.
Rammohan, Aravind
McKenzie, Matthew E.
Bidone, Tamara C.
Computational model of integrin adhesion elongation under an actin fiber
title Computational model of integrin adhesion elongation under an actin fiber
title_full Computational model of integrin adhesion elongation under an actin fiber
title_fullStr Computational model of integrin adhesion elongation under an actin fiber
title_full_unstemmed Computational model of integrin adhesion elongation under an actin fiber
title_short Computational model of integrin adhesion elongation under an actin fiber
title_sort computational model of integrin adhesion elongation under an actin fiber
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10325090/
https://www.ncbi.nlm.nih.gov/pubmed/37410718
http://dx.doi.org/10.1371/journal.pcbi.1011237
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