| Autor: |
Meddens MB; Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Geert Grooteplein Zuid 26-28, 6525 GA Nijmegen, The Netherlands., Pandzic E; Departments of Physics and Chemistry, McGill University Otto Maass (OM) Chemistry Building, 801 Sherbrooke Street West, Montreal, Quebec, Canada H3A 0B8., Slotman JA; Department of Pathology, Josephine Nefkens Institute, Erasmus MC, 3000 CA Rotterdam, The Netherlands., Guillet D; Departments of Physics and Chemistry, McGill University Otto Maass (OM) Chemistry Building, 801 Sherbrooke Street West, Montreal, Quebec, Canada H3A 0B8., Joosten B; Department of Cell Biology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Geert Grooteplein Zuid 26-28, 6525 GA Nijmegen, The Netherlands., Mennens S; Department of Cell Biology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Geert Grooteplein Zuid 26-28, 6525 GA Nijmegen, The Netherlands., Paardekooper LM; Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Geert Grooteplein Zuid 26-28, 6525 GA Nijmegen, The Netherlands., Houtsmuller AB; Department of Pathology, Josephine Nefkens Institute, Erasmus MC, 3000 CA Rotterdam, The Netherlands., van den Dries K; Department of Cell Biology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Geert Grooteplein Zuid 26-28, 6525 GA Nijmegen, The Netherlands., Wiseman PW; Departments of Physics and Chemistry, McGill University Otto Maass (OM) Chemistry Building, 801 Sherbrooke Street West, Montreal, Quebec, Canada H3A 0B8., Cambi A; Department of Cell Biology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Geert Grooteplein Zuid 26-28, 6525 GA Nijmegen, The Netherlands. |
| Abstrakt: |
Podosomes are cytoskeletal structures crucial for cell protrusion and matrix remodelling in osteoclasts, activated endothelial cells, macrophages and dendritic cells. In these cells, hundreds of podosomes are spatially organized in diversely shaped clusters. Although we and others established individual podosomes as micron-sized mechanosensing protrusive units, the exact scope and spatiotemporal organization of podosome clustering remain elusive. By integrating a newly developed extension of Spatiotemporal Image Correlation Spectroscopy with novel image analysis, we demonstrate that F-actin, vinculin and talin exhibit directional and correlated flow patterns throughout podosome clusters. Pattern formation and magnitude depend on the cluster actomyosin machinery. Indeed, nanoscopy reveals myosin IIA-decorated actin filaments interconnecting multiple proximal podosomes. Extending well-beyond podosome nearest neighbours, the actomyosin-dependent dynamic spatial patterns reveal a previously unappreciated mesoscale connectivity throughout the podosome clusters. This directional transport and continuous redistribution of podosome components provides a mechanistic explanation of how podosome clusters function as coordinated mechanosensory area. |
