Modular actin nano-architecture enables podosome protrusion and mechanosensing

Area of Science:

• Cell Biology
• Biophysics
• Biochemistry

Background:

• Invadosomes, including invadopodia and podosomes, are essential for basement membrane transmigration during embryonal development, tissue homeostasis, and tumor invasion.
• A detailed understanding of the structural framework enabling invadosome function, particularly podosome protrusion and mechanosensing, remains incomplete.

Purpose of the Study:

• To elucidate the modular actin nano-architecture of podosomes.
• To investigate how this architecture facilitates podosome protrusion and mechanosensing in response to substrate stiffness.

Main Methods:

• High-resolution imaging and biochemical analyses to characterize the actin organization within podosomes.
• Experimental manipulation of substrate stiffness to observe functional responses.

Main Results:

• Podosomes possess a modular actin nano-architecture comprising a central core (branched and linear actin modules) and radiating ventral (vinculin-bound) and dorsal (myosin IIA-crosslinked) filaments.
• On stiff substrates, podosomes exhibit long-range exploration and degradation; on compliant substrates, ventral filaments shorten, leading to short-range connectivity and non-degradative protrusion.
• Actin modularity dictates substrate exploration range and degradative behavior.

Conclusions:

• The study redefines the nanoscale architecture of podosomes, revealing a modular design.
• This modularity provides a paradigm for how actin-based structures enable cellular mechanosensing and regulate interactions with the extracellular matrix.
• Understanding this mechanism is critical for comprehending processes like tissue invasion and development.