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A mechanical model of cell segregation driven by differential adhesion.
William R Taylor1, Rosalind Morley, Alexey Krasavin
1Division of Mathematical Biology, MRC National Institute for Medical Research, London, United Kingdom. wtaylor@nimr.mrc.ac.uk
Plos One
|September 7, 2012
Summary
This study models cell segregation using mechanical forces, finding differential adhesion explains some experimental results but not faster Eph-ephrin signaling, suggesting additional mechanisms are involved in cell sorting.
Area of Science:
- Cell biology
- Biophysics
- Computational modeling
Background:
- Cell segregation is crucial for tissue development.
- Differential cell-cell adhesion is a known driver of cell sorting.
- Eph-ephrin signaling is implicated in cell-cell interactions.
Purpose of the Study:
- To investigate the role of mechanical forces and differential adhesion in cell segregation.
- To compare simulation results with experimental data from cell culture assays.
- To explore the contribution of Eph-ephrin interactions to cell sorting dynamics.
Main Methods:
- Simulations of two-cell type mixtures with contact-mediated linkage.
- Comparison of simulation outcomes with 2D cell culture experiments.
- Calibration of simulation time to experimental time scales.
- Analysis of segregation rates driven by differential adhesion versus Eph-ephrin signaling.
Main Results:
- The mechanical model accurately predicted segregation extent driven by differential adhesion in cadherin-expressing cells.
- Simulation time correlated within 50% of experimental time for differential adhesion.
- Differential adhesion simulations did not explain the rapid segregation observed with EphB2-ephrinB1 interactions.
- Eph-ephrin mediated segregation occurred an order of magnitude faster than predicted by differential adhesion alone.
Conclusions:
- Differential adhesion is a significant factor in cell segregation, as demonstrated by the mechanical model's agreement with experiments.
- The rapid cell segregation mediated by EphB2-ephrinB1 interactions indicates that mechanisms beyond simple differential adhesion are involved.
- Additional or alternative signaling pathways likely contribute to Eph-ephrin mediated cell sorting, highlighting the complexity of cell-cell communication.
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