Multi-scale modelling of the dynamics of cell colonies: insights into cell-adhesion forces and cancer invasion from in silico simulations

Daniela K. Schluter (Lead / Corresponding author), Ignacio Ramis-Conde, Mark A. J. Chaplain

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)
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Abstract

Studying the biophysical interactions between cells is crucial to understanding how normal tissue develops, how it is structured and also when malfunctions occur. Traditional experiments try to infer events at the tissue level after observing the behaviour of and interactions between individual cells. This approach assumes that cells behave in the same biophysical manner in isolated experiments as they do within colonies and tissues. In this paper, we develop a multi-scale multi-compartment mathematical model that accounts for the principal biophysical interactions and adhesion pathways not only at a cell–cell level but also at the level of cell colonies (in contrast to the traditional approach). Our results suggest that adhesion/separation forces between cells may be lower in cell colonies than traditional isolated single-cell experiments infer. As a consequence, isolated single-cell experiments may be insufficient to deduce important biological processes such as single-cell invasion after detachment from a solid tumour. The simulations further show that kinetic rates and cell biophysical characteristics such as pressure-related cell-cycle arrest have a major influence on cell colony patterns and can allow for the development of protrusive cellular structures as seen in invasive cancer cell lines independent of expression levels of pro-invasion molecules.
Original languageEnglish
Article number20141080
Pages (from-to)1-13
Number of pages13
JournalJournal of the Royal Society Interface
Volume12
Issue number103
Early online date17 Dec 2014
DOIs
Publication statusPublished - Feb 2015

Keywords

  • Individual-based modelling
  • Cell population modelling
  • Cell-adhesion forces
  • E-cadherin

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