Max Planck Institute for Medical Research, Heidelberg, Germany; Interdisciplinary Centre for Clinical Research, Aachen, Germany; DWI – Leibniz-Institute for Interactive Materials, Forckenbeckstrasse, Aachen, Germany; Institute of Molecular and Cellular Anatomy, RWTH Aachen University, Aachen, Germany
Jennifer L Young
Max Planck Institute for Medical Research, Heidelberg, Germany; Mechanobiology Institute, National University of Singapore, Singapore, Singapore; Department of Biomedical Engineering, National University of Singapore, Singapore, Singapore
Julian WR Wegner
Max Planck Institute for Medical Research, Heidelberg, Germany
Timmy Steins
Interdisciplinary Centre for Clinical Research, Aachen, Germany; Institute of Molecular and Cellular Anatomy, RWTH Aachen University, Aachen, Germany
Horst Kessler
Institute for Advance Study, Department of Chemistry, Technical University of Munich, Garching, Germany
Joachim P Spatz
Max Planck Institute for Medical Research, Heidelberg, Germany; Institute for Molecular System Engineering – IMSE - Heidelberg University, Heidelberg, Germany; Max Planck School Matter to Life, Heidelberg, Germany
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.
