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.

Additional Metadata
Persistent URL dx.doi.org/10.1038/s41467-019-13123-3, hdl.handle.net/1765/121686
Journal Nature Communications
Citation
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