Engineered Biomimetic Fibrillar Fibronectin Matrices Regulate Cell Adhesion Initiation, Migration, and Proliferation via α5β1 Integrin and Syndecan‐4 Crosstalk
Abstract Cells regulate adhesion to the fibrillar extracellular matrix (ECM) of which fibronectin is an essential component. However, most studies characterize cell adhesion to globular fibronectin substrates at time scales long after cells polarize and migrate. To overcome this limitation, a simple...
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Wiley
2023-08-01
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Series: | Advanced Science |
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Online Access: | https://doi.org/10.1002/advs.202300812 |
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author | Seungkuk Ahn Upnishad Sharma Krishna Chaitanya Kasuba Nico Strohmeyer Daniel J. Müller |
author_facet | Seungkuk Ahn Upnishad Sharma Krishna Chaitanya Kasuba Nico Strohmeyer Daniel J. Müller |
author_sort | Seungkuk Ahn |
collection | DOAJ |
description | Abstract Cells regulate adhesion to the fibrillar extracellular matrix (ECM) of which fibronectin is an essential component. However, most studies characterize cell adhesion to globular fibronectin substrates at time scales long after cells polarize and migrate. To overcome this limitation, a simple and scalable method to engineer biomimetic 3D fibrillar fibronectin matrices is introduced and how they are sensed by fibroblasts from the onset of attachment is characterized. Compared to globular fibronectin substrates, fibroblasts accelerate adhesion initiation and strengthening within seconds to fibrillar fibronectin matrices via α5β1 integrin and syndecan‐4. This regulation, which additionally accelerates on stiffened fibrillar matrices, involves actin polymerization, actomyosin contraction, and the cytoplasmic proteins paxillin, focal adhesion kinase, and phosphoinositide 3‐kinase. Furthermore, this immediate sensing and adhesion of fibroblast to fibrillar fibronectin guides migration speed, persistency, and proliferation range from hours to weeks. The findings highlight that fibrillar fibronectin matrices, compared to widely‐used globular fibronectin, trigger short‐ and long‐term cell decisions very differently and urge the use of such matrices to better understand in vivo interactions of cells and ECMs. The engineered fibronectin matrices, which can be printed onto non‐biological surfaces without loss of function, open avenues for various cell biological, tissue engineering and medical applications. |
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language | English |
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spelling | doaj.art-2bc434ae48e544ddbc350fdf3c327cdb2023-08-28T03:36:35ZengWileyAdvanced Science2198-38442023-08-011024n/an/a10.1002/advs.202300812Engineered Biomimetic Fibrillar Fibronectin Matrices Regulate Cell Adhesion Initiation, Migration, and Proliferation via α5β1 Integrin and Syndecan‐4 CrosstalkSeungkuk Ahn0Upnishad Sharma1Krishna Chaitanya Kasuba2Nico Strohmeyer3Daniel J. Müller4Department of Biosystems Science and Engineering Eidgenössische Technische Hochschule (ETH) Zurich Basel4058SwitzerlandDepartment of Biosystems Science and Engineering Eidgenössische Technische Hochschule (ETH) Zurich Basel4058SwitzerlandDepartment of Biosystems Science and Engineering Eidgenössische Technische Hochschule (ETH) Zurich Basel4058SwitzerlandDepartment of Biosystems Science and Engineering Eidgenössische Technische Hochschule (ETH) Zurich Basel4058SwitzerlandDepartment of Biosystems Science and Engineering Eidgenössische Technische Hochschule (ETH) Zurich Basel4058SwitzerlandAbstract Cells regulate adhesion to the fibrillar extracellular matrix (ECM) of which fibronectin is an essential component. However, most studies characterize cell adhesion to globular fibronectin substrates at time scales long after cells polarize and migrate. To overcome this limitation, a simple and scalable method to engineer biomimetic 3D fibrillar fibronectin matrices is introduced and how they are sensed by fibroblasts from the onset of attachment is characterized. Compared to globular fibronectin substrates, fibroblasts accelerate adhesion initiation and strengthening within seconds to fibrillar fibronectin matrices via α5β1 integrin and syndecan‐4. This regulation, which additionally accelerates on stiffened fibrillar matrices, involves actin polymerization, actomyosin contraction, and the cytoplasmic proteins paxillin, focal adhesion kinase, and phosphoinositide 3‐kinase. Furthermore, this immediate sensing and adhesion of fibroblast to fibrillar fibronectin guides migration speed, persistency, and proliferation range from hours to weeks. The findings highlight that fibrillar fibronectin matrices, compared to widely‐used globular fibronectin, trigger short‐ and long‐term cell decisions very differently and urge the use of such matrices to better understand in vivo interactions of cells and ECMs. The engineered fibronectin matrices, which can be printed onto non‐biological surfaces without loss of function, open avenues for various cell biological, tissue engineering and medical applications.https://doi.org/10.1002/advs.2023008123D fibrillar fibronectinadhesion initiationextracellular matrixintegrinspatiotemporal cell dynamicssyndecan |
spellingShingle | Seungkuk Ahn Upnishad Sharma Krishna Chaitanya Kasuba Nico Strohmeyer Daniel J. Müller Engineered Biomimetic Fibrillar Fibronectin Matrices Regulate Cell Adhesion Initiation, Migration, and Proliferation via α5β1 Integrin and Syndecan‐4 Crosstalk Advanced Science 3D fibrillar fibronectin adhesion initiation extracellular matrix integrin spatiotemporal cell dynamics syndecan |
title | Engineered Biomimetic Fibrillar Fibronectin Matrices Regulate Cell Adhesion Initiation, Migration, and Proliferation via α5β1 Integrin and Syndecan‐4 Crosstalk |
title_full | Engineered Biomimetic Fibrillar Fibronectin Matrices Regulate Cell Adhesion Initiation, Migration, and Proliferation via α5β1 Integrin and Syndecan‐4 Crosstalk |
title_fullStr | Engineered Biomimetic Fibrillar Fibronectin Matrices Regulate Cell Adhesion Initiation, Migration, and Proliferation via α5β1 Integrin and Syndecan‐4 Crosstalk |
title_full_unstemmed | Engineered Biomimetic Fibrillar Fibronectin Matrices Regulate Cell Adhesion Initiation, Migration, and Proliferation via α5β1 Integrin and Syndecan‐4 Crosstalk |
title_short | Engineered Biomimetic Fibrillar Fibronectin Matrices Regulate Cell Adhesion Initiation, Migration, and Proliferation via α5β1 Integrin and Syndecan‐4 Crosstalk |
title_sort | engineered biomimetic fibrillar fibronectin matrices regulate cell adhesion initiation migration and proliferation via α5β1 integrin and syndecan 4 crosstalk |
topic | 3D fibrillar fibronectin adhesion initiation extracellular matrix integrin spatiotemporal cell dynamics syndecan |
url | https://doi.org/10.1002/advs.202300812 |
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