Integrin Binding Dynamics Modulate Ligand-Specific Mechanosensing in Mammary Gland Fibroblasts

The link between integrin activity regulation and cellular mechanosensing of tissue rigidity, especially on different extracellular matrix ligands, remains poorly understood. Here, we find that primary mouse mammary gland stromal fibroblasts (MSFs) are able to spread efficiently, generate high force...

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Autores: Lerche, Martina, Elosegui Artola, Alberto, Kechagia, Jenny Z., Guzmán, Camilo, Georgiadou, Maria, Andreu, Ion, Gullberg, Donald, Roca-Cusachs Soulere, Pere, Peuhu, Emilia, Ivaska, Johanna
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/195118
Acceso en línea:https://hdl.handle.net/2445/195118
Access Level:acceso abierto
Palabra clave:Integrines
Mecanoteràpia
Glàndules mamàries
Fibroblasts
Integrins
Mechanotherapy
Mammary glands
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network_name_str España
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spelling Integrin Binding Dynamics Modulate Ligand-Specific Mechanosensing in Mammary Gland FibroblastsLerche, MartinaElosegui Artola, AlbertoKechagia, Jenny Z.Guzmán, CamiloGeorgiadou, MariaAndreu, IonGullberg, DonaldRoca-Cusachs Soulere, PerePeuhu, EmiliaIvaska, JohannaIntegrinesMecanoteràpiaGlàndules mamàriesFibroblastsIntegrinsMechanotherapyMammary glandsFibroblastsThe link between integrin activity regulation and cellular mechanosensing of tissue rigidity, especially on different extracellular matrix ligands, remains poorly understood. Here, we find that primary mouse mammary gland stromal fibroblasts (MSFs) are able to spread efficiently, generate high forces, and display nuclear YAP on soft collagen-coated substrates, resembling the soft mammary gland tissue. We describe that loss of the integrin inhibitor, SHARPIN, impedes MSF spreading specifically on soft type I collagen but not on fibronectin. Through quantitative experiments and computational modeling, we find that SHARPIN-deficient MSFs display faster force-induced unbinding of adhesions from collagen-coated beads. Faster unbinding, in turn, impairs force transmission in these cells, particularly, at the stiffness optimum observed for wild-type cells. Mechanistically, we link the impaired mechanotransduction of SHARPIN-deficient cells on collagen to reduced levels of collagen-binding integrin α11β1. Thus integrin activity regulation and α11β1 play a role in collagen-specific mechanosensing in MSFs.Elsevier2023202320202023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion25 p.application/pdfapplication/pdfhttps://hdl.handle.net/2445/195118Articles publicats en revistes (Biomedicina)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1016/j.isci.2020.100907iScience, 2020, vol. 23, num. 9, p. 100907https://doi.org/10.1016/j.isci.2020.100907cc-by nc-nd (c) Lerche, Martina et al., 2020http://creativecommons.org/licenses/by-nc-nd/3.0/es/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1951182026-05-29T05:05:01Z
dc.title.none.fl_str_mv Integrin Binding Dynamics Modulate Ligand-Specific Mechanosensing in Mammary Gland Fibroblasts
title Integrin Binding Dynamics Modulate Ligand-Specific Mechanosensing in Mammary Gland Fibroblasts
spellingShingle Integrin Binding Dynamics Modulate Ligand-Specific Mechanosensing in Mammary Gland Fibroblasts
Lerche, Martina
Integrines
Mecanoteràpia
Glàndules mamàries
Fibroblasts
Integrins
Mechanotherapy
Mammary glands
Fibroblasts
title_short Integrin Binding Dynamics Modulate Ligand-Specific Mechanosensing in Mammary Gland Fibroblasts
title_full Integrin Binding Dynamics Modulate Ligand-Specific Mechanosensing in Mammary Gland Fibroblasts
title_fullStr Integrin Binding Dynamics Modulate Ligand-Specific Mechanosensing in Mammary Gland Fibroblasts
title_full_unstemmed Integrin Binding Dynamics Modulate Ligand-Specific Mechanosensing in Mammary Gland Fibroblasts
title_sort Integrin Binding Dynamics Modulate Ligand-Specific Mechanosensing in Mammary Gland Fibroblasts
dc.creator.none.fl_str_mv Lerche, Martina
Elosegui Artola, Alberto
Kechagia, Jenny Z.
Guzmán, Camilo
Georgiadou, Maria
Andreu, Ion
Gullberg, Donald
Roca-Cusachs Soulere, Pere
Peuhu, Emilia
Ivaska, Johanna
author Lerche, Martina
author_facet Lerche, Martina
Elosegui Artola, Alberto
Kechagia, Jenny Z.
Guzmán, Camilo
Georgiadou, Maria
Andreu, Ion
Gullberg, Donald
Roca-Cusachs Soulere, Pere
Peuhu, Emilia
Ivaska, Johanna
author_role author
author2 Elosegui Artola, Alberto
Kechagia, Jenny Z.
Guzmán, Camilo
Georgiadou, Maria
Andreu, Ion
Gullberg, Donald
Roca-Cusachs Soulere, Pere
Peuhu, Emilia
Ivaska, Johanna
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Integrines
Mecanoteràpia
Glàndules mamàries
Fibroblasts
Integrins
Mechanotherapy
Mammary glands
Fibroblasts
topic Integrines
Mecanoteràpia
Glàndules mamàries
Fibroblasts
Integrins
Mechanotherapy
Mammary glands
Fibroblasts
description The link between integrin activity regulation and cellular mechanosensing of tissue rigidity, especially on different extracellular matrix ligands, remains poorly understood. Here, we find that primary mouse mammary gland stromal fibroblasts (MSFs) are able to spread efficiently, generate high forces, and display nuclear YAP on soft collagen-coated substrates, resembling the soft mammary gland tissue. We describe that loss of the integrin inhibitor, SHARPIN, impedes MSF spreading specifically on soft type I collagen but not on fibronectin. Through quantitative experiments and computational modeling, we find that SHARPIN-deficient MSFs display faster force-induced unbinding of adhesions from collagen-coated beads. Faster unbinding, in turn, impairs force transmission in these cells, particularly, at the stiffness optimum observed for wild-type cells. Mechanistically, we link the impaired mechanotransduction of SHARPIN-deficient cells on collagen to reduced levels of collagen-binding integrin α11β1. Thus integrin activity regulation and α11β1 play a role in collagen-specific mechanosensing in MSFs.
publishDate 2020
dc.date.none.fl_str_mv 2020
2023
2023
2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/195118
url https://hdl.handle.net/2445/195118
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1016/j.isci.2020.100907
iScience, 2020, vol. 23, num. 9, p. 100907
https://doi.org/10.1016/j.isci.2020.100907
dc.rights.none.fl_str_mv cc-by nc-nd (c) Lerche, Martina et al., 2020
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by nc-nd (c) Lerche, Martina et al., 2020
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 25 p.
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv Articles publicats en revistes (Biomedicina)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,81155

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