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Dynamic fibronectin assembly and remodeling by leader neural crest cells prevents jamming in collective cell migration

Collective cell migration plays an essential role in vertebrate development, yet the extent to which dynamically changing microenvironments influence this phenomenon remains unclear. Observations of the distribution of the extracellular matrix (ECM) component fibronectin during the migration of loos...

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Autores principales: Martinson, William Duncan, McLennan, Rebecca, Teddy, Jessica M, McKinney, Mary C, Davidson, Lance A, Baker, Ruth E, Byrne, Helen M, Kulesa, Paul M, Maini, Philip K
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10198726/
https://www.ncbi.nlm.nih.gov/pubmed/37073859
http://dx.doi.org/10.7554/eLife.83792
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author Martinson, William Duncan
McLennan, Rebecca
Teddy, Jessica M
McKinney, Mary C
Davidson, Lance A
Baker, Ruth E
Byrne, Helen M
Kulesa, Paul M
Maini, Philip K
author_facet Martinson, William Duncan
McLennan, Rebecca
Teddy, Jessica M
McKinney, Mary C
Davidson, Lance A
Baker, Ruth E
Byrne, Helen M
Kulesa, Paul M
Maini, Philip K
author_sort Martinson, William Duncan
collection PubMed
description Collective cell migration plays an essential role in vertebrate development, yet the extent to which dynamically changing microenvironments influence this phenomenon remains unclear. Observations of the distribution of the extracellular matrix (ECM) component fibronectin during the migration of loosely connected neural crest cells (NCCs) lead us to hypothesize that NCC remodeling of an initially punctate ECM creates a scaffold for trailing cells, enabling them to form robust and coherent stream patterns. We evaluate this idea in a theoretical setting by developing an individual-based computational model that incorporates reciprocal interactions between NCCs and their ECM. ECM remodeling, haptotaxis, contact guidance, and cell-cell repulsion are sufficient for cells to establish streams in silico, however, additional mechanisms, such as chemotaxis, are required to consistently guide cells along the correct target corridor. Further model investigations imply that contact guidance and differential cell-cell repulsion between leader and follower cells are key contributors to robust collective cell migration by preventing stream breakage. Global sensitivity analysis and simulated gain- and loss-of-function experiments suggest that long-distance migration without jamming is most likely to occur when leading cells specialize in creating ECM fibers, and trailing cells specialize in responding to environmental cues by upregulating mechanisms such as contact guidance.
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spelling pubmed-101987262023-05-20 Dynamic fibronectin assembly and remodeling by leader neural crest cells prevents jamming in collective cell migration Martinson, William Duncan McLennan, Rebecca Teddy, Jessica M McKinney, Mary C Davidson, Lance A Baker, Ruth E Byrne, Helen M Kulesa, Paul M Maini, Philip K eLife Computational and Systems Biology Collective cell migration plays an essential role in vertebrate development, yet the extent to which dynamically changing microenvironments influence this phenomenon remains unclear. Observations of the distribution of the extracellular matrix (ECM) component fibronectin during the migration of loosely connected neural crest cells (NCCs) lead us to hypothesize that NCC remodeling of an initially punctate ECM creates a scaffold for trailing cells, enabling them to form robust and coherent stream patterns. We evaluate this idea in a theoretical setting by developing an individual-based computational model that incorporates reciprocal interactions between NCCs and their ECM. ECM remodeling, haptotaxis, contact guidance, and cell-cell repulsion are sufficient for cells to establish streams in silico, however, additional mechanisms, such as chemotaxis, are required to consistently guide cells along the correct target corridor. Further model investigations imply that contact guidance and differential cell-cell repulsion between leader and follower cells are key contributors to robust collective cell migration by preventing stream breakage. Global sensitivity analysis and simulated gain- and loss-of-function experiments suggest that long-distance migration without jamming is most likely to occur when leading cells specialize in creating ECM fibers, and trailing cells specialize in responding to environmental cues by upregulating mechanisms such as contact guidance. eLife Sciences Publications, Ltd 2023-04-19 /pmc/articles/PMC10198726/ /pubmed/37073859 http://dx.doi.org/10.7554/eLife.83792 Text en © 2023, Martinson et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Computational and Systems Biology
Martinson, William Duncan
McLennan, Rebecca
Teddy, Jessica M
McKinney, Mary C
Davidson, Lance A
Baker, Ruth E
Byrne, Helen M
Kulesa, Paul M
Maini, Philip K
Dynamic fibronectin assembly and remodeling by leader neural crest cells prevents jamming in collective cell migration
title Dynamic fibronectin assembly and remodeling by leader neural crest cells prevents jamming in collective cell migration
title_full Dynamic fibronectin assembly and remodeling by leader neural crest cells prevents jamming in collective cell migration
title_fullStr Dynamic fibronectin assembly and remodeling by leader neural crest cells prevents jamming in collective cell migration
title_full_unstemmed Dynamic fibronectin assembly and remodeling by leader neural crest cells prevents jamming in collective cell migration
title_short Dynamic fibronectin assembly and remodeling by leader neural crest cells prevents jamming in collective cell migration
title_sort dynamic fibronectin assembly and remodeling by leader neural crest cells prevents jamming in collective cell migration
topic Computational and Systems Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10198726/
https://www.ncbi.nlm.nih.gov/pubmed/37073859
http://dx.doi.org/10.7554/eLife.83792
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