Integrin Binding Dynamics Modulate Ligand-Specific Mechanosensing in Mammary Gland Fibroblasts
Summary: 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 h...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-03-01
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| Series: | iScience |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004220300912 |
| _version_ | 1818030193219993600 |
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| author | Martina Lerche Alberto Elosegui-Artola Jenny Z. Kechagia Camilo Guzmán Maria Georgiadou Ion Andreu Donald Gullberg Pere Roca-Cusachs Emilia Peuhu Johanna Ivaska |
| author_facet | Martina Lerche Alberto Elosegui-Artola Jenny Z. Kechagia Camilo Guzmán Maria Georgiadou Ion Andreu Donald Gullberg Pere Roca-Cusachs Emilia Peuhu Johanna Ivaska |
| author_sort | Martina Lerche |
| collection | DOAJ |
| description | Summary: 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. : Biological Sciences; Cell Biology; Functional Aspects of Cell Biology Subject Areas: Biological Sciences, Cell Biology, Functional Aspects of Cell Biology |
| first_indexed | 2024-12-10T05:31:41Z |
| format | Article |
| id | doaj.art-41c77b2087c94c2883d7883f77e81399 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-12-10T05:31:41Z |
| publishDate | 2020-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-41c77b2087c94c2883d7883f77e813992022-12-22T02:00:31ZengElsevieriScience2589-00422020-03-01233Integrin Binding Dynamics Modulate Ligand-Specific Mechanosensing in Mammary Gland FibroblastsMartina Lerche0Alberto Elosegui-Artola1Jenny Z. Kechagia2Camilo Guzmán3Maria Georgiadou4Ion Andreu5Donald Gullberg6Pere Roca-Cusachs7Emilia Peuhu8Johanna Ivaska9Turku Bioscience Centre, University of Turku and Åbo Akademi University, FI-20520 Turku, FinlandInstitute for Bioengineering of Catalonia, University of Barcelona, Barcelona 08028, SpainInstitute for Bioengineering of Catalonia, University of Barcelona, Barcelona 08028, SpainTurku Bioscience Centre, University of Turku and Åbo Akademi University, FI-20520 Turku, FinlandTurku Bioscience Centre, University of Turku and Åbo Akademi University, FI-20520 Turku, FinlandInstitute for Bioengineering of Catalonia, University of Barcelona, Barcelona 08028, SpainUniversity of Bergen, 5020 Bergen, NorwayInstitute for Bioengineering of Catalonia, University of Barcelona, Barcelona 08028, Spain; University of Barcelona, Barcelona 08028, SpainTurku Bioscience Centre, University of Turku and Åbo Akademi University, FI-20520 Turku, Finland; Institute of Biomedicine and Cancer Research Laboratory FICAN West, University of Turku, FI-20520 Turku, Finland; Corresponding authorTurku Bioscience Centre, University of Turku and Åbo Akademi University, FI-20520 Turku, Finland; Department of Biochemistry, University of Turku, FI-20520 Turku, Finland; Corresponding authorSummary: 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. : Biological Sciences; Cell Biology; Functional Aspects of Cell Biology Subject Areas: Biological Sciences, Cell Biology, Functional Aspects of Cell Biologyhttp://www.sciencedirect.com/science/article/pii/S2589004220300912 |
| spellingShingle | Martina Lerche Alberto Elosegui-Artola Jenny Z. Kechagia Camilo Guzmán Maria Georgiadou Ion Andreu Donald Gullberg Pere Roca-Cusachs Emilia Peuhu Johanna Ivaska Integrin Binding Dynamics Modulate Ligand-Specific Mechanosensing in Mammary Gland Fibroblasts iScience |
| title | 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_short | Integrin Binding Dynamics Modulate Ligand-Specific Mechanosensing in Mammary Gland Fibroblasts |
| title_sort | integrin binding dynamics modulate ligand specific mechanosensing in mammary gland fibroblasts |
| url | http://www.sciencedirect.com/science/article/pii/S2589004220300912 |
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