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Integrin α5β1 nano-presentation regulates collective keratinocyte migration independent of substrate rigidity

View ORCID ProfileJacopo Di Russo, Jennifer L. Young, Julian W. R. Wegner, Timmy Steins, Horst Kessler, View ORCID ProfileJoachim P. Spatz
doi: https://doi.org/10.1101/2021.03.08.434437
Jacopo Di Russo
1Max Planck Institute for Medical Research, Jahnstrasse 29, 69120 Heidelberg, Germany
2Interdisciplinary Centre for Clinical Research, Pauwelstrasse 30, RWTH Aachen University, 52074 Aachen, Germany
3DWI – Leibniz-Institute for Interactive Materials, Forckenbeckstrasse 50, 52074 Aachen, Germany
4Institute of Molecular and Cellular Anatomy, RWTH Aachen University, Wendlingweg 2, 52074 Aachen, Germany
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  • For correspondence: [email protected] [email protected]
Jennifer L. Young
1Max Planck Institute for Medical Research, Jahnstrasse 29, 69120 Heidelberg, Germany
5Mechanobiology Institute, National University of Singapore, 5A Engineering Drive 1, Singapore 117411
6Department of Biomedical Engineering, National University of Singapore, 4 Engineering Drive 3, Singapore 117583
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Julian W. R. Wegner
1Max Planck Institute for Medical Research, Jahnstrasse 29, 69120 Heidelberg, Germany
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Timmy Steins
2Interdisciplinary Centre for Clinical Research, Pauwelstrasse 30, RWTH Aachen University, 52074 Aachen, Germany
4Institute of Molecular and Cellular Anatomy, RWTH Aachen University, Wendlingweg 2, 52074 Aachen, Germany
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Horst Kessler
7Institute for Advance Study, Department of Chemistry, Technical University of Munich, 85748, Garching, Germany
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Joachim P. Spatz
1Max Planck Institute for Medical Research, Jahnstrasse 29, 69120 Heidelberg, Germany
8Institute for Molecular System Engineering – IMSE - Heidelberg University, Germany
9Max Planck School Matter to Life
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  • For correspondence: [email protected] [email protected]
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Abstract

Nanometer-scale properties of the extracellular matrix influence many biological processes, including cell motility. While much information is available for single cell migration, to date, no knowledge exists on how the nanoscale presentation of extracellular matrix receptors influences collective cell migration. In wound healing, basal keratinocytes collectively migrate on a fibronectin-rich provisional basement membrane to re-epithelialize the injured skin. Among other receptors, the fibronectin receptor integrin α5β1 plays a pivotal role in this process. Using a highly specific integrin α5β1 peptidomimetic combined with nanopatterned hydrogels, we show that keratinocyte sheets regulate their migration ability at an optimal integrin α5β1 nanospacing. This efficiency relies on the effective propagation of stresses within the cell monolayer independent of substrate stiffness. For the first time, this work highlights the importance of extracellular matrix receptor nanoscale organization required for efficient tissue regeneration.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • The manuscript has been corrected for minor missing information. Supplementary figure 1 has been corrected.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
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Posted March 25, 2021.
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Integrin α5β1 nano-presentation regulates collective keratinocyte migration independent of substrate rigidity
Jacopo Di Russo, Jennifer L. Young, Julian W. R. Wegner, Timmy Steins, Horst Kessler, Joachim P. Spatz
bioRxiv 2021.03.08.434437; doi: https://doi.org/10.1101/2021.03.08.434437
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Integrin α5β1 nano-presentation regulates collective keratinocyte migration independent of substrate rigidity
Jacopo Di Russo, Jennifer L. Young, Julian W. R. Wegner, Timmy Steins, Horst Kessler, Joachim P. Spatz
bioRxiv 2021.03.08.434437; doi: https://doi.org/10.1101/2021.03.08.434437

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