From confinement to remodeling: modeling topotaxis-driven cell migration in obstacles networks.

Area of Science:

• Biophysics
• Computational Biology
• Cell Biology

Background:

• Cell migration through the extracellular matrix (ECM) is crucial for physiological and pathological processes.
• Topographical features of the ECM, like fiber alignment, influence cell movement via topotaxis.
• Understanding these guidance mechanisms requires simplified, tractable models.

Purpose of the Study:

• To develop a minimal particle-based model of single-cell motility in 2D fibrous environments.
• To investigate the impact of topographical constraints, cell behaviors, and ECM remodeling on migration efficiency.
• To provide mechanistic insights into topotaxis and anomalous transport in confined spaces.

Main Methods:

• A 2D particle-based model simulating cell motility in an abstracted network of obstacles.
• Integration of chemotaxis, stochastic polarity, steric repulsion, trapping escape strategies, and obstacle remodeling.
• Simulation of heterogeneous obstacle repulsion and local obstacle displacement due to cell contact.

Main Results:

• Active remodeling of obstacles consistently improved migration efficiency and target acquisition.
• Escape strategies offered partial improvement, while heterogeneity introduced directional variability.
• Cell trajectories exhibited effective diffusion at long timescales but nontrivial deviations at intermediate dynamics.

Conclusions:

• Cell migration in fibrous environments is significantly enhanced by active ECM remodeling.
• The model provides a framework for understanding interactions between confinement, transport, and remodeling in topotaxis.
• Further studies can incorporate cell deformation and more complex ECM architectures.