Active Traction Force Response to Long-Term Cyclic Stretch Is Dependent on Cell Pre-stress

Area of Science:

• Biomedical Engineering
• Cellular Mechanobiology
• Tissue Engineering

Background:

• Mechanical stimulation profoundly influences cell functions like proliferation and differentiation.
• Understanding cell-generated traction force under long-term stretch is crucial but understudied.
• Cellular pre-stress is a key factor influencing cellular response to mechanical stimuli.

Purpose of the Study:

• To investigate how cells alter traction force in response to long-term cyclic stretch.
• To determine the role of initial cell pre-stress in modulating this response.
• To explore the effects of substrate stiffness and biochemical cues on cell mechanics.

Main Methods:

• Developed a novel method to assess cell traction force after 24-hour cyclic uniaxial or biaxial stretch.
• Utilized stiff (7.5 kPa) and soft (0.6 kPa) polyacrylamide gels to control cell pre-stress.
• Manipulated cell pre-stress using blebbistatin and transforming growth factor β1 (TGF-β1) treatment.

Main Results:

• Cells on stiff substrates with high pre-stress decreased traction force and spread area under stretch.
• Cells on soft substrates with low pre-stress significantly increased traction force and spread area.
• TGF-β1 treatment increased pre-stress and traction force drop, while myosin II inhibition increased force.
• Cellular reorientation was observed, typically perpendicular to the stretch direction, except in myosin II inhibited cells.

Conclusions:

• Cellular traction force response to long-term cyclic stretch is critically dependent on initial cell pre-stress.
• High pre-stress leads to force reduction via actin stress fiber depolymerization.
• Low pre-stress leads to force increase via actin cytoskeleton reinforcement.
• Findings offer insights into mechanotransduction and tissue remodeling processes.