Forces generated by lamellipodial actin filament elongation regulate the WAVE complex during cell migration

Area of Science:

• Cell Biology
• Biophysics
• Mechanobiology

Background:

• Actin filaments generate forces crucial for cellular processes like migration and endocytosis.
• Actin network structure is regulated by mechanical forces, but forces acting on regulators at assembly sites remain uncharacterized.

Purpose of the Study:

• To demonstrate forces acting on actin regulators at actin assembly sites.
• To investigate the mechanical control of WAVE regulatory complex (WRC) dynamics and Arp2/3 complex activation by actin filament elongation.

Main Methods:

• Single-protein tracking to observe WRC dynamics.
• Optical tweezers to apply piconewton forces to WRC.
• WRC crosslinking to inhibit mechanical dissociation.

Main Results:

• Actin filament elongation drives WRC lateral movements and turnover at the lamellipodium tip.
• Piconewton forces from filament elongation dissociate WRC from the lamellipodium tip.
• WRC trapping, dwell time, and binding strength correlate with its activation.
• Hindering WRC dissociation increases dwell time and Arp2/3-dependent membrane protrusion.

Conclusions:

• Local forces from actin filament elongation mechanically regulate WRC turnover and Arp2/3 complex activity.
• This mechanical feedback mechanism tunes regulator activity during cell migration.