Collective migration during a gap closure in a two-dimensional haptotactic model

Abstract The ability of cells to respond to substrate-bound protein gradients is crucial for many physiological processes, such as immune response, neurogenesis and cancer cell migration. However, the difficulty to produce well-controlled protein gradients has long been a limitation to our understan...

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Autores principales:	Marie Versaevel, Laura Alaimo, Valentine Seveau, Marine Luciano, Danahe Mohammed, Céline Bruyère, Eléonore Vercruysse, Olivier Théodoly, Sylvain Gabriele
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8ca1f2c2cb344d9d839a71cb6cb285e2
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spelling	oai:doaj.org-article:8ca1f2c2cb344d9d839a71cb6cb285e22021-12-02T13:31:11ZCollective migration during a gap closure in a two-dimensional haptotactic model10.1038/s41598-021-84998-w2045-2322https://doaj.org/article/8ca1f2c2cb344d9d839a71cb6cb285e22021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84998-whttps://doaj.org/toc/2045-2322Abstract The ability of cells to respond to substrate-bound protein gradients is crucial for many physiological processes, such as immune response, neurogenesis and cancer cell migration. However, the difficulty to produce well-controlled protein gradients has long been a limitation to our understanding of collective cell migration in response to haptotaxis. Here we use a photopatterning technique to create circular, square and linear fibronectin (FN) gradients on two-dimensional (2D) culture substrates. We observed that epithelial cells spread preferentially on zones of higher FN density, creating rounded or elongated gaps within epithelial tissues over circular or linear FN gradients, respectively. Using time-lapse experiments, we demonstrated that the gap closure mechanism in a 2D haptotaxis model requires a significant increase of the leader cell area. In addition, we found that gap closures are slower on decreasing FN densities than on homogenous FN-coated substrate and that fresh closed gaps are characterized by a lower cell density. Interestingly, our results showed that cell proliferation increases in the closed gap region after maturation to restore the cell density, but that cell–cell adhesive junctions remain weaker in scarred epithelial zones. Taken together, our findings provide a better understanding of the wound healing process over protein gradients, which are reminiscent of haptotaxis.Marie VersaevelLaura AlaimoValentine SeveauMarine LucianoDanahe MohammedCéline BruyèreEléonore VercruysseOlivier ThéodolySylvain GabrieleNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Marie Versaevel Laura Alaimo Valentine Seveau Marine Luciano Danahe Mohammed Céline Bruyère Eléonore Vercruysse Olivier Théodoly Sylvain Gabriele Collective migration during a gap closure in a two-dimensional haptotactic model
description	Abstract The ability of cells to respond to substrate-bound protein gradients is crucial for many physiological processes, such as immune response, neurogenesis and cancer cell migration. However, the difficulty to produce well-controlled protein gradients has long been a limitation to our understanding of collective cell migration in response to haptotaxis. Here we use a photopatterning technique to create circular, square and linear fibronectin (FN) gradients on two-dimensional (2D) culture substrates. We observed that epithelial cells spread preferentially on zones of higher FN density, creating rounded or elongated gaps within epithelial tissues over circular or linear FN gradients, respectively. Using time-lapse experiments, we demonstrated that the gap closure mechanism in a 2D haptotaxis model requires a significant increase of the leader cell area. In addition, we found that gap closures are slower on decreasing FN densities than on homogenous FN-coated substrate and that fresh closed gaps are characterized by a lower cell density. Interestingly, our results showed that cell proliferation increases in the closed gap region after maturation to restore the cell density, but that cell–cell adhesive junctions remain weaker in scarred epithelial zones. Taken together, our findings provide a better understanding of the wound healing process over protein gradients, which are reminiscent of haptotaxis.
format	article
author	Marie Versaevel Laura Alaimo Valentine Seveau Marine Luciano Danahe Mohammed Céline Bruyère Eléonore Vercruysse Olivier Théodoly Sylvain Gabriele
author_facet	Marie Versaevel Laura Alaimo Valentine Seveau Marine Luciano Danahe Mohammed Céline Bruyère Eléonore Vercruysse Olivier Théodoly Sylvain Gabriele
author_sort	Marie Versaevel
title	Collective migration during a gap closure in a two-dimensional haptotactic model
title_short	Collective migration during a gap closure in a two-dimensional haptotactic model
title_full	Collective migration during a gap closure in a two-dimensional haptotactic model
title_fullStr	Collective migration during a gap closure in a two-dimensional haptotactic model
title_full_unstemmed	Collective migration during a gap closure in a two-dimensional haptotactic model
title_sort	collective migration during a gap closure in a two-dimensional haptotactic model
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/8ca1f2c2cb344d9d839a71cb6cb285e2
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Collective migration during a gap closure in a two-dimensional haptotactic model

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