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

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.

A genome-wide screen identifies YAP/WBP2 interplay conferring growth advantage on human epidermal stem cells

“…Consistent with computational simulations demonstrating that the rate of adherens junction turnover can be a major determinant of colony growth53, we found that impairment of adherens junction homoeostasis by inhibition of Rho GTPase signalling54 with the Rho kinase (ROCK) inhibitor Y-27632 promoted colony expansion (Fig. 7b,c).…”

Computational modeling of single‐cell mechanics and cytoskeletal mechanobiology

“…For example, Bambardekar et al proposed and validated a continuum viscoelastic constitutive equation to describe the force dynamics at epithelial cell–cell adhesions, while Coburn et al used a particle‐based method, known as the vertex‐based method, to simulate the acto‐myosin contractile forces that transmit across the tissue through the cell–cell adhesions. Tightly coupled with experimental data, these models have helped to estimate tensions at the cell–cell adhesion interface and could therefore be adopted for studies on the role of cell–cell adhesions on single‐cell mechanobiology. Thanks to these many advances in measuring and modeling cell–cell adhesions and their acto‐myosin generated forces, research in this field is now focused on uncovering how these mechanical forces regulate cellular and tissue remodeling.…”

Mathematical modelling of angiogenesis using continuous cell-based models

“…Regarding cancer initiation, growth and invasion of cancer cells, and the use of cell-based modelling, we refer to the studies by Schlüter et al. (2014) and Vermolen et al. (2015).…”