Shear forces induce ICAM-1 nanoclustering on endothelial cells that impact on T-cell migration |
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Authors: | Izabela K Piechocka Sarah Keary Alberto Sosa-Costa Lukas Lau Nitin Mohan Jelena Stanisavljevic Kyra JE Borgman Melike Lakadamyali Carlo Manzo Maria F Garcia-Parajo |
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Institution: | 1. ICFO-Institut de Ciencies Fotoniques, The Barcelona Institute of Science and Technology, Barcelona, Spain;2. Department of Biosystems and Soft Matter, Institute of Fundamental Technological Research, Polish Academy of Sciences, Warsaw, Poland;3. Department of Biological Sciences and Bioengineering, Indian Institute of Technology, Kanpur, India;4. Institut Curie, PSL Research University, CNRS UMR3664, Chromatin Dynamics lab, Paris, France;5. Perelman School of Medicine, Department of Physiology, University of Pennsylvania, Philadelphia, Pennsylvania;6. Universitat de Vic-Universitat Central de Catalunya (UVic-UCC), Vic, Spain;7. ICREA, Barcelona, Spain |
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Abstract: | The leukocyte-specific β2-integrin LFA-1 and its ligand ICAM-1, expressed on endothelial cells (ECs), are involved in the arrest, adhesion, and transendothelial migration of leukocytes. Although the role of mechanical forces on LFA-1 activation is well established, the impact of forces on its major ligand ICAM-1 has received less attention. Using a parallel-plate flow chamber combined with confocal and super-resolution microscopy, we show that prolonged shear flow induces global translocation of ICAM-1 on ECs upstream of flow direction. Interestingly, shear forces caused actin rearrangements and promoted actin-dependent ICAM-1 nanoclustering before LFA-1 engagement. T cells adhered to mechanically prestimulated ECs or nanoclustered ICAM-1 substrates developed a promigratory phenotype, migrated faster, and exhibited shorter-lived interactions with ECs than when adhered to non mechanically stimulated ECs or to monomeric ICAM-1 substrates. Together, our results indicate that shear forces increase ICAM-1/LFA-1 bonds because of ICAM-1 nanoclustering, strengthening adhesion and allowing cells to exert higher traction forces required for faster migration. Our data also underscore the importance of mechanical forces regulating the nanoscale organization of membrane receptors and their contribution to cell adhesion regulation. |
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