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

Rachele Allena1,2

  • 1Laboratoire Jean Alexandre Dieudonné CNRS UMR7351, Université Côte d'Azur, Nice, France. rachele.allena@univ-cotedazur.fr.

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Cell migration in fibrous environments is guided by physical cues. Active remodeling of the extracellular matrix (ECM) significantly enhances cell movement efficiency and target finding, surpassing simple escape strategies.

Keywords:
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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.