Podosome Dynamics and Extracellular Matrix Interaction

Podosomes are dynamic, actin-based protrusive structures that mediate cell–matrix interactions in a range of professional and non-professional migratory cells. They consist of a dense, branched actin core surrounded by a ring of adhesion molecules and adaptor proteins, enabling local matrix degradation and force transduction. Through cycles of actin polymerisation and myosin-driven contractility, podosomes probe the mechanical properties of the extracellular matrix (ECM), coordinate collective behaviours, and facilitate processes such as immune surveillance, tissue remodelling and angiogenesis. Oscillatory protrusion–retraction dynamics generate chemo-mechanical waves that propagate across podosome clusters, while integrin-mediated tensile forces in the piconewton range underpin mechanosensing of substrate stiffness. On compliant surfaces, changes in actin nano-architecture modulate connectivity between cores, tuning degradative versus exploratory modes of behaviour. Such adaptability underlies the global significance of podosome function in wound healing, cancer invasion and vascular sprouting, and presents potential targets for therapeutic modulation of cell migration and matrix remodelling.

Research from Nature Portfolio

Recent studies have developed a chemo-mechanical framework describing how actin polymerisation, myosin contractility and monomer diffusion interact to drive both individual oscillations and wave-like coordination in podosome clusters, revealing that microenvironment stiffness modulates these dynamics and validating predictions through pharmacological perturbations. Advanced tension-probe technologies have mapped integrin-generated forces around podosome cores with piconewton sensitivity, demonstrating a ring of tensile stresses that couple to protrusive forces and mediate substrate mechanosensing. High-resolution imaging has further defined a modular actin nano-architecture in podosomes, with distinct branched and linear actin modules radiating into ventral and dorsal filaments, which remodel in response to substrate rigidity to regulate long-range connectivity, degradative activity and mechanosensory feedback.

Podosome Dynamics and Extracellular Matrix Interaction publication trend

The graph below shows the total number of articles in podosome dynamics and extracellular matrix interaction across all publications each year (not limited to Nature Index journals).

Technical terms

Podosome: A dynamic, actin-rich membrane protrusion surrounded by adhesion proteins that mediates adhesion, force transduction and local matrix degradation.

Extracellular matrix (ECM): A complex network of proteins and polysaccharides that provides structural support and biochemical signals to surrounding cells.

Actin polymerisation: The process of assembling monomeric actin into filamentous networks that drive protrusive force generation.

Integrin: A transmembrane adhesion receptor that links the ECM to the cytoskeleton and transduces mechanical signals.

Mechanosensing: The ability of cells to detect and respond to mechanical properties of their environment through force-mediated signalling pathways.

References

1. Chemo-mechanical diffusion waves explain collective dynamics of immune cell podosomes. Nature Communications (2023).
2. Mesenchymal Migration on Adhesive–Nonadhesive Alternate Surfaces in Macrophages. Advanced Science (2023).
3. DNA mechanotechnology reveals that integrin receptors apply pN forces in podosomes on fluid substrates. Nature Communications (2019).
4. Modular actin nano-architecture enables podosome protrusion and mechanosensing. Nature Communications (2019).
5. VEGF-A/Notch-Induced Podosomes Proteolyse Basement Membrane Collagen-IV during Retinal Sprouting Angiogenesis. Cell Reports (2016).