A mechanistic motor-clutch model that explains cell shape dynamics to cyclic stretch

Area of Science:

• Cell Biology
• Biophysics
• Computational Biology

Background:

• Cells in the body are exposed to cyclic mechanical loading, influencing their processes and shape.
• In vitro studies show cells reorient when their substrate is cyclically stretched.

Purpose of the Study:

• To computationally model the mechanisms underlying cell reorientation in response to cyclic mechanical stretch.
• To investigate how factors like substrate stiffness and stretch frequency affect cell alignment.

Main Methods:

• Adapted existing computational models of the actin-myosin-integrin motor-clutch system.
• Developed a new computational model to simulate cell behavior under cyclic substrate stretch.

Main Results:

• The model predicts actin bundle alignment perpendicular to stretch direction under typical conditions.
• Under specific conditions (e.g., low substrate stiffness), actin bundles align parallel to stretch.
• Stretch frequency influences reorientation rate, and myosin function is crucial for this response.

Conclusions:

• Computational predictions align with existing literature and new experimental data.
• Cell alignment direction under various stretching conditions can be explained by cell-substrate detachment events during substrate stretching or relaxation.