title: Actomyosin-dependent dynamic spatial patterns of cytoskeletal components drive mesoscale podosome organization.
abstract: 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.
authors.affiliation: Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Geert Grooteplein Zuid 26-28, 6525 GA Nijmegen, The Netherlands.
authors.forename: Marjolein B M
authors.initials: MB
authors.lastname: Meddens
authors.affiliation: Departments of Physics and Chemistry, McGill University Otto Maass (OM) Chemistry Building, 801 Sherbrooke Street West, Montreal, Quebec, Canada H3A 0B8.
authors.forename: Elvis
authors.initials: E
authors.lastname: Pandzic
authors.affiliation: Department of Pathology, Josephine Nefkens Institute, Erasmus MC, 3000 CA Rotterdam, The Netherlands.
authors.forename: Johan A
authors.identifier: 0000-0001-9705-9620
authors.initials: JA
authors.lastname: Slotman
authors.affiliation: Departments of Physics and Chemistry, McGill University Otto Maass (OM) Chemistry Building, 801 Sherbrooke Street West, Montreal, Quebec, Canada H3A 0B8.
authors.forename: Dominique
authors.initials: D
authors.lastname: Guillet
authors.affiliation: Department of Cell Biology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Geert Grooteplein Zuid 26-28, 6525 GA Nijmegen, The Netherlands.
authors.forename: Ben
authors.initials: B
authors.lastname: Joosten
authors.affiliation: Department of Cell Biology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Geert Grooteplein Zuid 26-28, 6525 GA Nijmegen, The Netherlands.
authors.forename: Svenja
authors.initials: S
authors.lastname: Mennens
authors.affiliation: Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Geert Grooteplein Zuid 26-28, 6525 GA Nijmegen, The Netherlands.
authors.forename: Laurent M
authors.identifier: 0000-0001-7079-2697
authors.initials: LM
authors.lastname: Paardekooper
authors.affiliation: Department of Pathology, Josephine Nefkens Institute, Erasmus MC, 3000 CA Rotterdam, The Netherlands.
authors.forename: Adriaan B
authors.initials: AB
authors.lastname: Houtsmuller
authors.affiliation: Department of Cell Biology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Geert Grooteplein Zuid 26-28, 6525 GA Nijmegen, The Netherlands.
authors.forename: Koen
authors.initials: K
authors.lastname: van den Dries
authors.affiliation: Departments of Physics and Chemistry, McGill University Otto Maass (OM) Chemistry Building, 801 Sherbrooke Street West, Montreal, Quebec, Canada H3A 0B8.
authors.forename: Paul W
authors.identifier: 0000-0002-5732-2858
authors.initials: PW
authors.lastname: Wiseman
authors.affiliation: Department of Cell Biology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Geert Grooteplein Zuid 26-28, 6525 GA Nijmegen, The Netherlands.
authors.forename: Alessandra
authors.identifier: 0000-0003-1597-1582
authors.initials: A
authors.lastname: Cambi
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D000205:Actomyosin / Q000378:metabolism*; D022081:Cell Surface Extensions / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism*; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D024507:Nonmuscle Myosin Type IIA / Q000378:metabolism; D000069261:Podosomes / Q000378:metabolism*; D058105:Polymerization; D012212:Rheology; D016608:Talin / Q000378:metabolism; D013997:Time Factors; D016596:Vinculin / Q000378:metabolism
chemical_list: D000199:Actins; D016608:Talin; D016596:Vinculin; D000205:Actomyosin; D024507:Nonmuscle Myosin Type IIA