A thermodynamically motivated model for stress-fiber reorganization

Area of Science:

• Cellular mechanics
• Biophysics
• Computational biology

Background:

• Cellular mechanical properties are crucial for tissue development and disease.
• Stress fibers, composed of actin and myosin, play a key role in cell contractility and force generation.
• Understanding stress-fiber dynamics under mechanical loading is essential for cell biology.

Purpose of the Study:

• To develop a comprehensive model for stress-fiber reorganization and contractility.
• To investigate the influence of mechanical loading (stress, strain, strain rate) on stress-fiber dynamics.
• To explain previously contradictory experimental observations regarding cell behavior under cyclic loading.

Main Methods:

• A 3D computational model incorporating stress-fiber formation, dissociation, and remodeling kinetics.
• Model kinetics are based on the enthalpies of actin/myosin functional units.
• Inclusion of unbound stress-fiber protein transport and analysis under various cyclic loading conditions.

Main Results:

• The model predicts stress-fiber alignment perpendicular to strain in 2D and parallel in 3D at 10% strain and 1 Hz.
• At lower frequencies, 2D cells show strain waveform sensitivity only with asymmetric loading (fast lengthening, slow shortening).
• At very low frequencies (mHz), 2D cells align perpendicular to strain above a critical amplitude.

Conclusions:

• The developed model successfully explains diverse cell responses to cyclic mechanical stimuli.
• It highlights the importance of dimensionality (2D vs. 3D) and loading characteristics in dictating cell mechanical behavior.
• This work provides a framework for predicting cell reorganization under complex mechanical environments.