Intermediate filament-deficient cells are mechanically softer at large deformation: a multi-scale simulation study

Area of Science:

• Cell biology
• Biophysics
• Computational modeling

Background:

• The cell cytoskeleton provides structure and shape via proteins like microtubules, actin microfilaments, and intermediate filaments.
• Intermediate filaments are hypothesized to be essential for cellular mechanical stability.

Purpose of the Study:

• To investigate the role of intermediate filaments in cell mechanical behavior using a computational model.
• To understand how varying intermediate filament densities affect cell deformation and mechanical properties.

Main Methods:

• Development of a simple coarse-grained computational model for intermediate filament networks in eukaryotic cells.
• Simulation of cell deformation under varying intermediate filament densities.
• Comparison of simulation results with experimental data from vimentin-deficient cells.

Main Results:

• Intermediate filament-deficient cells exhibit softer mechanical responses at large deformations.
• Cellular mechanical properties are largely unchanged under small deformations.
• Increased intermediate filament density alters the cell nucleus's deformation, causing greater stretch and orthogonal contraction.

Conclusions:

• Intermediate filaments significantly contribute to cell stiffness and deformation, maintaining structural integrity under stress.
• The computational model provides mechanistic insights into cell mechanics and nuclear deformation.
• The model serves as a basis for future research on disease states and structural changes affecting biomechanics.