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 exper-
iments infer. As a consequence, isolated single-cell experiments may be
insufficient to deduce important biological processes such as single-cell inva-
sion 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.
Date of Acceptance : 25/11/2014
c 2014 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited