Single cell active force generation under dynamic loading - Part II: Active modelling insights.

Area of Science:

• Cellular biomechanics
• Computational biology
• Biophysics

Background:

• Single-cell force-strain responses to cyclic loading are complex.
• Understanding these responses requires mechanistic analysis of active stress generation and actin cytoskeleton remodeling.
• Previous models often use passive material laws unsuitable for untreated contractile cells.

Purpose of the Study:

• To develop an active bio-chemo-mechanical model for simulating untreated contractile cells.
• To incorporate stress fiber (SF) remodeling and active tension generation.
• To explain the complex force-strain behavior observed in single-cell AFM experiments.

Main Methods:

• Developed a novel active bio-chemo-mechanical model.
• Incorporated a fading memory SF contractility model.
• Simulated cell responses to cyclic loading, analyzing forces generated by different SF orientations.

Main Results:

• The active model accurately captures transient cell responses to dynamic loading.
• Axially oriented SFs generate tension during unloading, explaining high stretching forces.
• Hoop-oriented SFs generate tension during loading, explaining compression resistance.
• Passive visco-hyperelastic models are inappropriate for untreated contractile cells.

Conclusions:

• The active modeling framework provides a coherent understanding of single-cell biomechanics.
• The model explains experimentally observed complex force generation patterns.
• Passive models should be restricted to simulations of chemically disrupted cells lacking active force generation.