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Published on: October 25, 2018
Matrix geometry determines optimal cancer cell migration strategy and modulates response to interventions
Melda Tozluoğlu1, Alexander L Tournier, Robert P Jenkins
1Biomolecular Modelling Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
Nature Cell Biology
|June 25, 2013
Summary
Cell migration models predict how matrix geometry affects cell movement. Adhesion is not essential for cell migration in confined environments, and models accurately predict responses to drug treatments.
Area of Science:
- Cell Biology
- Biophysics
- Computational Biology
Background:
- Cell migration is crucial for development and disease, but its mechanisms are complex and influenced by the extracellular matrix (ECM).
- Predicting cell migration strategies and responses to perturbations is challenging due to variations in matrix geometry and molecular requirements.
Purpose of the Study:
- To develop a comprehensive biophysical model of cell motility.
- To investigate the theoretical requirements for rapid cell migration across diverse ECM geometries.
- To predict the effects of experimental interventions on cell migration in various environments.
Main Methods:
- A computational model integrating actin polymerization, contractility, membrane blebbing, and cell-ECM adhesion was developed.
- The model was used to simulate cell migration in different matrix geometries, including confined and discontinuous environments.
- Model predictions were validated against in vivo intravital imaging and in vitro experimental data involving kinase inhibitors and integrin depletion.
Main Results:
- Matrix geometry significantly alters the relationship between cell adhesion, contractility, and migration velocity.
- Cell-matrix adhesion was found to be dispensable for migration in discontinuous confined environments.
- The model successfully predicted the in vivo and in vitro responses to various pharmacological and genetic perturbations.
Conclusions:
- Cell migration is highly adaptable to ECM geometry, with distinct molecular requirements in confined spaces.
- A unified biophysical model can accurately predict cell migration dynamics and responses to interventions.
- This work provides a framework for understanding and predicting cell migration in complex biological contexts.
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