mDia1 senses both force and torque during F-actin filament polymerization

Area of Science:

• Cell Biology
• Biophysics
• Molecular Biology

Background:

• Formins are key regulators of actin dynamics, crucial for cellular processes.
• They polymerize actin filaments by binding to the barbed end via a ring-like structure of FH2 domains.
• It is hypothesized that mechanical force influences formin conformation and activity.

Purpose of the Study:

• To investigate the effect of mechanical force on mDia1-mediated actin polymerization.
• To determine if formin (mDia1) senses torque in addition to force.

Main Methods:

• Single-actin filament stretching using magnetic tweezers.
• Measurement of actin polymerization rates under varying forces (0.5–10 pN).
• Assessment of force-promoted polymerization under torsionally constrained and unconstrained conditions.

Main Results:

• Increasing force from 0.5 to 10 pN significantly accelerated mDia1-dependent actin polymerization.
• Force-promoted polymerization was observed only when the actin filament was torsionally unconstrained.
• This suggests mDia1 is sensitive to both force and torque.

Conclusions:

• Mechanical force can enhance actin polymerization rates regulated by formins (mDia1).
• Formin (mDia1) likely senses and responds to torsional stress in actin filaments.
• These findings offer insights into how cells utilize mechanical cues to regulate actin organization.