Comparison of cell migration mechanical strategies in three-dimensional matrices: a computational study

Area of Science:

• Cell Biology
• Biophysics
• Computational Biology

Background:

• Cell migration on 2D surfaces follows a well-defined protrusion-contraction cycle.
• In 3D environments, cell migration strategies are diverse and depend on cell type and extracellular matrix (ECM) properties.

Purpose of the Study:

• To classify and model diverse cell migration strategies in 3D environments.
• To understand the role of actin dynamics, ECM properties, and adhesion in dictating cell motility modes.

Main Methods:

• Utilized computer simulations to model cell migration in three-dimensional environments.
• Varied parameters including proteolysis, adhesion dynamics, and spatial distributions of cellular components.
• Analyzed spatial-temporal dynamics of actin protrusion, actin-myosin contraction, and actin-ECM adhesion.

Main Results:

• Developed a model capable of reproducing six experimentally observed cell motility modes: mesenchymal, chimneying, amoeboid, blebbing, finger-like protrusion, and rear-squeezing.
• Demonstrated that cell motility mode evolves with changes in ECM density and adhesion detachment rate.
• Identified key factors influencing cell speed, including adhesion strength, ECM elasticity, and mesh size.

Conclusions:

• The study provides a unified framework for understanding diverse cell migration strategies in 3D.
• The findings highlight the critical interplay between cellular internal dynamics and the physical properties of the extracellular matrix.
• The model offers predictive power for cell speed based on biophysical parameters, with implications for tissue development and disease.