Lamellipodium tip actin barbed ends serve as a force sensor.

Area of Science:

• Cell Biology
• Biophysics

Background:

• Cells migrate directionally by sensing environmental rigidity and traction forces.
• The precise molecular mechanisms underlying this force sensing remain unclear.

Purpose of the Study:

• To investigate the role of tip actin barbed ends as force sensors in directed cell migration.
• To elucidate the mechanism by which cells sense and respond to mechanical forces during protrusion.

Main Methods:

• Developed a novel method to visualize intracellular single-molecule fluorescent actin dynamics using an elastic culture substrate.
• Applied controlled substrate stretches to observe cellular responses in real-time.
• Quantified actin assembly rates and load changes at the lamellipodium tip.

Main Results:

• Actin assembly at the lamellipodium tip increased immediately after cell edge stretch, with rates dependent on stretch speed.
• Actin polymerization remained elevated during a sustained hold phase, correlating with decreased load on tip barbed ends.
• Stretch-induced actin polymerization occurred independently of the WAVE complex and Ena/VASP proteins.
• Observed relationships between force and actin polymerization align with the Brownian ratchet mechanism.

Conclusions:

• Tip actin barbed ends function as active force sensors, directly coupling actin assembly to load reduction.
• This mechanism allows cells to sense mechanical forces and mediate directed cell protrusion.
• The findings provide new insights into the biophysical regulation of cell migration.