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.,
Nature Communications
Department of Pathology

van den Dries, K. (Koen), Nahidiazar, L. (Leila), Slotman, J. A., Meddens, M.B.M. (Marjolein B M), Pandzic, E. (Elvis), Joosten, B., … Cambi, A. (2019). Modular actin nano-architecture enables podosome protrusion and mechanosensing. Nature Communications, 10(1). doi:10.1038/s41467-019-13123-3