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.
Highlights
Traditional experiments for understanding the influence of cell adhesion on tissue structure may be classified into two principal groups
We assume that effective adhesion complexes at the cell membrane can be directly re-organized to form bonds at different locations by a transport process within the cell membrane [9]. This implies that almost the total number of possible E-cadherin–b-catenin complexes can be employed at a single cell–cell contact site, but as soon as contact is made with another cell, the complexes are redistributed
Ciþ is the number of E-cadherin–b-catenin complexes that are translocated from other cell–cell contact sites to the site of contact with cell i, and CiÀ is the number of complexes that is moved from cell–cell contact site i to other contact sites
Summary
Traditional experiments for understanding the influence of cell adhesion on tissue structure may be classified into two principal groups. The question arises whether conclusions can be drawn and extrapolated to cellular behaviour at the colony level from the forces measured in isolated cell assays To approach this question, we propose a multi-scale—multi-compartment model that captures the biophysical essentials of the cell-adhesion system and relates intracellular and intercellular phenotypic characteristics to cell culture systems. The model is developed by testing simulation results of various hypotheses for the explicit structure of the adhesion pathway and cell–cell interactions against given cell colony data. In contrast to the earlier model developed by Ramis-Conde et al [5], including compartmentalization provides for spatial heterogeneity of the adhesion proteins This new feature is essential to understand whether it is plausible to extrapolate conclusions from isolated cell experiments to the cell colony level as it allows us to compare cell–cell adhesion forces between individual cells in a colony with forces measured between pairs of isolated cells in micro-pipette assays
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
