Engineered Biomimetic Fibrillar Fibronectin Matrices Regulate Cell Adhesion Initiation, Migration, and Proliferation via α5β1 Integrin and Syndecan-4 Crosstalk
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Date
2023-08-25
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Journal Article
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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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published
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Volume
10 (24)
Pages / Article No.
2300812
Publisher
Wiley-VCH
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Subject
3D fibrillar fibronectin; adhesion initiation; extracellular matrix; integrin; spatiotemporal cell dynamics; syndecan
Organisational unit
03870 - Müller, Daniel J. / Müller, Daniel J.
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Funding
182587 - Characterizing the cell cycle dependent regulation of adhesion to extracellular matrix proteins (SNF)
215690 - Characterizing molecular mechanisms by which cells sense extracellular matrices differentially to regulate adhesion and growth (SNF)
215690 - Characterizing molecular mechanisms by which cells sense extracellular matrices differentially to regulate adhesion and growth (SNF)
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