Chemo-mechanical diffusion waves explain collective dynamics of immune cell podosomes

Area of Science:

• Cell Biology
• Biophysics
• Immunology

Background:

• Immune cells like macrophages and dendritic cells use podosomes, which are actin-rich protrusions, for force generation, migration, and antigen surveillance.
• Podosomes exhibit individual height oscillations and coordinated wave-like dynamics within clusters, but the underlying mechanisms are not fully understood.

Purpose of the Study:

• To develop a chemo-mechanical model explaining the dynamics of podosomes in clusters.
• To elucidate the mechanisms governing individual podosome oscillations and collective wave-like coordination.

Main Methods:

• Integrated actin polymerization, myosin contractility, actin diffusion, and mechanosensitive signaling into a theoretical model.
• Validated model predictions using pharmacological treatments and varying microenvironment stiffness.

Main Results:

• Podosome oscillatory growth occurs when actin polymerization and myosin contraction rates are similar.
• Actin monomer diffusion is identified as the driver for wave-like coordination of podosome oscillations.

Conclusions:

• The developed chemo-mechanical model provides a framework for understanding podosome dynamics.
• This research offers insights into immune cell mechanosensing in processes like wound healing and cancer immunotherapy.