Cyclic Force Applied to FAs Induces Actin Recruitment Depending on the Dynamic Loading Pattern

Area of Science:

• Cell Biology
• Biophysics
• Mechanobiology

Background:

• Mechanical forces on focal adhesions (FAs) are crucial for cytoskeletal reorganization.
• The impact of the temporal pattern of these forces on cellular behavior remains largely unknown.

Purpose of the Study:

• To investigate endothelial cell responses to locally applied cyclic forces on focal adhesions.
• To elucidate the role of force temporal patterns, including frequency and duty cycle, in cellular signaling.

Main Methods:

• Utilized a novel electromagnetic tweezer system to apply controlled cyclic forces (0.1-10 Hz, 0-100% duty cycle) to magnetic microbeads coated with fibronectin on endothelial cells.
• Monitored actin recruitment around focal adhesions in response to varying force patterns.
• Assessed the influence of myosin activity by modifying it.

Main Results:

• Specific cyclic force patterns (1-2 Hz, 25-50% duty cycle) significantly increased actin recruitment around focal adhesions.
• This enhanced actin recruitment was dependent on myosin activity, as it diminished upon modification.
• Demonstrated that focal adhesion sensitivity to force timing is linked to their viscoelastic properties.

Conclusions:

• The temporal pattern of mechanical forces, not just their magnitude, significantly impacts cellular responses at focal adhesions.
• Myosin activity and the viscoelastic properties of focal adhesions are key determinants in sensing and responding to the timing of applied forces.