Multi-Step Extracellular Matrix Remodelling and Stiffening in the Development of Idiopathic Pulmonary Fibrosis
The extracellular matrix (ECM) of the lung is a filamentous network composed mainly of collagens, elastin, and proteoglycans that provides structural and physical support to its populating cells. Proliferation, migration and overall behaviour of those cells is greatly determined by micromechanical q...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/2/1708 |
| _version_ | 1797441068826886144 |
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| author | Constança Júnior Anna Ulldemolins Maria Narciso Isaac Almendros Ramon Farré Daniel Navajas Javier López Mar Eroles Felix Rico Núria Gavara |
| author_facet | Constança Júnior Anna Ulldemolins Maria Narciso Isaac Almendros Ramon Farré Daniel Navajas Javier López Mar Eroles Felix Rico Núria Gavara |
| author_sort | Constança Júnior |
| collection | DOAJ |
| description | The extracellular matrix (ECM) of the lung is a filamentous network composed mainly of collagens, elastin, and proteoglycans that provides structural and physical support to its populating cells. Proliferation, migration and overall behaviour of those cells is greatly determined by micromechanical queues provided by the ECM. Lung fibrosis displays an aberrant increased deposition of ECM which likely changes filament organization and stiffens the ECM, thus upregulating the profibrotic profile of pulmonary cells. We have previously used AFM to assess changes in the Young’s Modulus (E) of the ECM in the lung. Here, we perform further ECM topographical, mechanical and viscoelastic analysis at the micro- and nano-scale throughout fibrosis development. Furthermore, we provide nanoscale correlations between topographical and elastic properties of the ECM fibres. Firstly, we identify a softening of the ECM after rats are instilled with media associated with recovery of mechanical homeostasis, which is hindered in bleomycin-instilled lungs. Moreover, we find opposite correlations between fibre stiffness and roughness in PBS- vs bleomycin-treated lung. Our findings suggest that changes in ECM nanoscale organization take place at different stages of fibrosis, with the potential to help identify pharmacological targets to hinder its progression. |
| first_indexed | 2024-03-09T12:17:35Z |
| format | Article |
| id | doaj.art-3513bab5794048f99361dc49e7b1f140 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T12:17:35Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-3513bab5794048f99361dc49e7b1f1402023-11-30T22:44:28ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-01-01242170810.3390/ijms24021708Multi-Step Extracellular Matrix Remodelling and Stiffening in the Development of Idiopathic Pulmonary FibrosisConstança Júnior0Anna Ulldemolins1Maria Narciso2Isaac Almendros3Ramon Farré4Daniel Navajas5Javier López6Mar Eroles7Felix Rico8Núria Gavara9Unitat de Biofísica i Bioenginyeria, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, 08036 Barcelona, SpainUnitat de Biofísica i Bioenginyeria, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, 08036 Barcelona, SpainUnitat de Biofísica i Bioenginyeria, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, 08036 Barcelona, SpainUnitat de Biofísica i Bioenginyeria, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, 08036 Barcelona, SpainUnitat de Biofísica i Bioenginyeria, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, 08036 Barcelona, SpainUnitat de Biofísica i Bioenginyeria, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, 08036 Barcelona, SpainInstitut Pasteur de Lille, U1019-UMR9017-CIIL-Centre d’Infection et d’Immunité de Lille, Université de Lille, CNRS, Inserm, CHU Lille, 59000 Lille, FranceAix-Marseille, CNRS, INSERM, LAI, Centuri Centre for Living Systems, 13009 Marseille, FranceAix-Marseille, CNRS, INSERM, LAI, Centuri Centre for Living Systems, 13009 Marseille, FranceUnitat de Biofísica i Bioenginyeria, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, 08036 Barcelona, SpainThe extracellular matrix (ECM) of the lung is a filamentous network composed mainly of collagens, elastin, and proteoglycans that provides structural and physical support to its populating cells. Proliferation, migration and overall behaviour of those cells is greatly determined by micromechanical queues provided by the ECM. Lung fibrosis displays an aberrant increased deposition of ECM which likely changes filament organization and stiffens the ECM, thus upregulating the profibrotic profile of pulmonary cells. We have previously used AFM to assess changes in the Young’s Modulus (E) of the ECM in the lung. Here, we perform further ECM topographical, mechanical and viscoelastic analysis at the micro- and nano-scale throughout fibrosis development. Furthermore, we provide nanoscale correlations between topographical and elastic properties of the ECM fibres. Firstly, we identify a softening of the ECM after rats are instilled with media associated with recovery of mechanical homeostasis, which is hindered in bleomycin-instilled lungs. Moreover, we find opposite correlations between fibre stiffness and roughness in PBS- vs bleomycin-treated lung. Our findings suggest that changes in ECM nanoscale organization take place at different stages of fibrosis, with the potential to help identify pharmacological targets to hinder its progression.https://www.mdpi.com/1422-0067/24/2/1708extracellular matrixatomic force microscopymechanosensingidiopathic pulmonary fibrosis |
| spellingShingle | Constança Júnior Anna Ulldemolins Maria Narciso Isaac Almendros Ramon Farré Daniel Navajas Javier López Mar Eroles Felix Rico Núria Gavara Multi-Step Extracellular Matrix Remodelling and Stiffening in the Development of Idiopathic Pulmonary Fibrosis International Journal of Molecular Sciences extracellular matrix atomic force microscopy mechanosensing idiopathic pulmonary fibrosis |
| title | Multi-Step Extracellular Matrix Remodelling and Stiffening in the Development of Idiopathic Pulmonary Fibrosis |
| title_full | Multi-Step Extracellular Matrix Remodelling and Stiffening in the Development of Idiopathic Pulmonary Fibrosis |
| title_fullStr | Multi-Step Extracellular Matrix Remodelling and Stiffening in the Development of Idiopathic Pulmonary Fibrosis |
| title_full_unstemmed | Multi-Step Extracellular Matrix Remodelling and Stiffening in the Development of Idiopathic Pulmonary Fibrosis |
| title_short | Multi-Step Extracellular Matrix Remodelling and Stiffening in the Development of Idiopathic Pulmonary Fibrosis |
| title_sort | multi step extracellular matrix remodelling and stiffening in the development of idiopathic pulmonary fibrosis |
| topic | extracellular matrix atomic force microscopy mechanosensing idiopathic pulmonary fibrosis |
| url | https://www.mdpi.com/1422-0067/24/2/1708 |
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