Polymerization force-regulated actin filament-Arp2/3 complex interaction dominates self-adaptive cell migrations.

Area of Science:

• Cell Biology
• Biophysics
• Computational Biology

Background:

• Cell migration is crucial for cancer invasion and immune responses.
• Understanding the molecular mechanisms driving cell adaptation to heterogeneous microenvironments is limited.
• Experimental probing of millisecond-scale protein dynamics in cell migration is challenging.

Purpose of the Study:

• To establish a theory and multiscale modeling system explaining how cells adapt migration to complex extracellular microenvironments (ECMs).
• To elucidate the molecular interactions governing self-adaptive cell propulsion and morphological changes.

Main Methods:

• Developed a spatiotemporal
• resistance-adaptive propulsion
• theory.
• Created a multiscale dynamic modeling system from protein interactions to whole-cell behavior.
• Analyzed the roles of Arp2/3 complexes and actin filament dynamics.

Main Results:

• Cells self-adapt propulsive forces to heterogeneous ECMs via resistance-triggered positive and negative feedback mechanisms.
• Positive feedback, driven by actin filament bending and Arp2/3 binding, enhances propulsion.
• Negative feedback hinders branched filament assembly in high-resistance areas, enabling obstacle circumvention.
• Cell migration velocity exhibits temporal hysteresis due to cytoskeleton remodeling.
• Directional migration depends on ECM stiffness and local actin polymerization rates.

Conclusions:

• The interplay between polymerization force, actin filaments, and Arp2/3 complex binding dictates self-adaptive cell migration.
• The developed theory and model provide predictive insights into cell movement dynamics in complex ECMs.
• Synergistic feedback mechanisms confer powerful, flexible migration and efficient protein utilization.