Free energy analysis of cell spreading

Area of Science:

• Cell biology
• Biophysics
• Computational modeling

Background:

• Cell spreading is a fundamental biological process.
• The role of physical forces and energy minimization in cell spreading is not fully understood.
• Existing models do not fully capture the interplay between cytoskeletal dynamics and cell adhesion.

Purpose of the Study:

• To develop and implement a steady-state computational model for cell spreading.
• To investigate the hypothesis that free energy minimization drives cell spreading.
• To explore the influence of substrate properties on cell spreading dynamics.

Main Methods:

• Developed a steady-state adaptation of a thermodynamically motivated stress fiber (SF) model.
• Utilized a non-local finite element setting.
• Incorporated conservation laws for cytoskeletal proteins and cell membrane integrins.
• Simulated cell spreading under varying substrate stiffness and ligand densities.

Main Results:

• Cell spreading is driven by a balance between decreasing cytoskeletal free energy and increasing passive elastic free energy.
• Lower spread area observed on compliant substrates compared to rigid ones.
• Reduced substrate ligand density limits cell spreading.
• Model predictions align with experimental data (Engler et al., 2003).
• Simulated cell deformation on patterned substrates (Théry et al., 2006) shows stress fiber distribution consistent with experimental observations.

Conclusions:

• Cell spreading is a thermodynamically driven process governed by free energy minimization.
• The model accurately predicts the impact of substrate stiffness and ligand density on cell spreading.
• The distribution of stress fibers in spread cells is explained by energy minimization principles.