Adhesion modulates cell morphology and migration within dense fibrous networks

Area of Science:

• Biophysics
• Cell Biology
• Computational Biology

Background:

• Active cell migration is fundamental for multicellular organisms, involved in development and immune responses.
• Cancer cell invasion and metastasis rely on mechanical strategies to navigate tissue barriers.
• Understanding cell migration in complex microenvironments is critical for disease research.

Purpose of the Study:

• To investigate the influence of mechanical interactions, specifically spatial restriction and adhesion, on cell migration.
• To develop and validate a novel computational model for simulating cell migration in dense fibrous media.
• To compare simulation results with experimental data from *in vitro* cell migration assays.

Main Methods:

• Utilized a phase-field model and dissipative particle dynamics for simulating cell migration.
• Quantified cell velocity and morphology as a function of fiber density and cell-matrix adhesion.
• Validated the computational model by comparing simulation outcomes with existing experimental migration assays of fibrosarcoma cells.

Main Results:

• Cell migration is significantly affected by mechanical interactions, particularly adhesion, in crowded environments.
• Increased cell-matrix adhesion enhances cell velocity and modulates cell morphology.
• Matrix metalloproteinases (MMPs) were identified as important modulators of cell adhesion during migration.

Conclusions:

• Minimalist computational models can effectively capture key features of cell migration in fibrous matrices.
• Adhesion is a critical factor in cell migration, influencing both speed and shape.
• Further experimental studies are recommended to elucidate the role of specific MMPs in confined cell migration.