TY - JOUR

T1 - Multi-scale modelling of the dynamics of cell colonies

T2 - insights into cell-adhesion forces and cancer invasion from in silico simulations

AU - Schlueter, Daniela K.

AU - Ramis-Conde, Ignacio

AU - Chaplain, Mark A. J.

N1 - 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

PY - 2015/2

Y1 - 2015/2

N2 - Studying the biophysical interactions between cells is crucial to understandinghow normal tissue develops, how it is structured and also when malfunctionsoccur. Traditional experiments try to infer events at the tissue level afterobserving the behaviour of and interactions between individual cells. Thisapproach assumes that cells behave in the same biophysical manner in isolatedexperiments as they do within colonies and tissues. In this paper, we develop amulti-scale multi-compartment mathematical model that accounts for theprincipal biophysical interactions and adhesion pathways not only at a cell–cell level but also at the level of cell colonies (in contrast to the traditionalapproach). Our results suggest that adhesion/separation forces betweencells may be lower in cell colonies than traditional isolated single-cell exper-iments infer. As a consequence, isolated single-cell experiments may beinsufficient to deduce important biological processes such as single-cell inva-sion after detachment from a solid tumour. The simulations further show thatkinetic rates and cell biophysical characteristics such as pressure-related cell-cycle arrest have a major influence on cell colony patterns and can allow forthe development of protrusive cellular structures as seen in invasive cancercell lines independent of expression levels of pro-invasion molecules.

AB - Studying the biophysical interactions between cells is crucial to understandinghow normal tissue develops, how it is structured and also when malfunctionsoccur. Traditional experiments try to infer events at the tissue level afterobserving the behaviour of and interactions between individual cells. Thisapproach assumes that cells behave in the same biophysical manner in isolatedexperiments as they do within colonies and tissues. In this paper, we develop amulti-scale multi-compartment mathematical model that accounts for theprincipal biophysical interactions and adhesion pathways not only at a cell–cell level but also at the level of cell colonies (in contrast to the traditionalapproach). Our results suggest that adhesion/separation forces betweencells may be lower in cell colonies than traditional isolated single-cell exper-iments infer. As a consequence, isolated single-cell experiments may beinsufficient to deduce important biological processes such as single-cell inva-sion after detachment from a solid tumour. The simulations further show thatkinetic rates and cell biophysical characteristics such as pressure-related cell-cycle arrest have a major influence on cell colony patterns and can allow forthe development of protrusive cellular structures as seen in invasive cancercell lines independent of expression levels of pro-invasion molecules.

U2 - 10.1098/rsif.2014.1080

DO - 10.1098/rsif.2014.1080

M3 - Journal article

VL - 12

JO - Interface

JF - Interface

SN - 1742-5689

IS - 103

ER -