TY - JOUR T1 - Modular actin nano-architecture enables podosome protrusion and mechanosensing JF - bioRxiv DO - 10.1101/583492 SP - 583492 AU - Koen van den Dries AU - Leila Nahidiazar AU - Johan A. Slotman AU - Marjolein B.M. Meddens AU - Elvis Pandzic AU - Ben Joosten AU - Marleen Ansems AU - Joost Schouwstra AU - Anke Meijer AU - Raymond Steen AU - Mietske Wijers AU - Jack Fransen AU - Adriaan B. Houtsmuller AU - Paul W. Wiseman AU - Kees Jalink AU - Alessandra cambi Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/03/20/583492.abstract N2 - Basement membrane transmigration during embryonal development, tissue homeostasis and tumor invasion relies on invadosomes, a collective term for invadopodia and podosomes. An adequate structural framework for this process is still missing. Here, we reveal the modular actin nano-architecture that enables podosome protrusion and mechanosensing. The podosome protrusive core contains a central branched actin module encased by a linear actin module, each harboring specific actin interactors and actin isoforms. From the core, two actin modules radiate: ventral filaments bound by vinculin and connected to the plasma membrane and dorsal interpodosomal filaments crosslinked by myosin IIA. On stiff substrates, the actin modules mediate long-range substrate exploration, associated with degradative behavior. On compliant substrates, the vinculin-bound ventral actin filaments shorten, resulting in short-range connectivity and a focally protrusive, non-degradative state. Our findings redefine podosome nanoscale architecture and reveal a paradigm for how actin modularity drives invadosome mechanosensing in cells that breach tissue boundaries. ER -