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

Schlüter DK, Ramis-Conde I, Chaplain MA - J R Soc Interface (2014)

Bottom Line: This approach assumes that cells behave in the same biophysical manner in isolated experiments as they do within colonies and tissues.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.

View Article: PubMed Central - PubMed

Affiliation: Division of Mathematics, The University of Dundee, Dundee, UK dkschlueter@maths.dundee.ac.uk.

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.

Show MeSH

Related in: MedlinePlus

Schematic diagram showing the E-cadherin–β-catenin dynamics as considered in the Model 1 [(a)] and Model 2 [(a) + (b)]. Free E-cadherin (E) and β-catenin (β) in the cytoplasm bind to form a complex (E/β). In adherent cells, in addition to the general transport to the cell surface, E-cadherin–β-catenin complexes are trafficked to the contact area. If the complex is transported to a site of cell–cell contact (denoted  at cell contact site i), it can bind complexes on the neighbouring cell's surface. If there is no binding partner, the complex can be internalized again and recycled. The same process takes place when bonds are broken due to junction disassembly. Whereas in Model 1, the amount of E-cadherin–β-catenin complexes that can be trafficked to one cell–cell contact site is limited, Model 2 comprises of additional dynamics such that the E-cadherin–β-catenin complexes are redistributed between contact sites when a cell has got more than one neighbouring cell as is shown in (b). (Online version in colour.)
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4305411&req=5

RSIF20141080F1: Schematic diagram showing the E-cadherin–β-catenin dynamics as considered in the Model 1 [(a)] and Model 2 [(a) + (b)]. Free E-cadherin (E) and β-catenin (β) in the cytoplasm bind to form a complex (E/β). In adherent cells, in addition to the general transport to the cell surface, E-cadherin–β-catenin complexes are trafficked to the contact area. If the complex is transported to a site of cell–cell contact (denoted at cell contact site i), it can bind complexes on the neighbouring cell's surface. If there is no binding partner, the complex can be internalized again and recycled. The same process takes place when bonds are broken due to junction disassembly. Whereas in Model 1, the amount of E-cadherin–β-catenin complexes that can be trafficked to one cell–cell contact site is limited, Model 2 comprises of additional dynamics such that the E-cadherin–β-catenin complexes are redistributed between contact sites when a cell has got more than one neighbouring cell as is shown in (b). (Online version in colour.)

Mentions: Endocytosis is followed by the disruption of the E-cadherin–β-catenin complex and the components can either be degraded, recycled for cell–cell adhesion or re-used in different signalling contexts. As production of neither E-cadherin nor β-catenin is explicitly taken into account, the possibility of degradation is also not considered in the model but it is assumed that the overall number of molecules is at a steady state. The model dynamics are shown in figure 1.Figure 1.


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

Schlüter DK, Ramis-Conde I, Chaplain MA - J R Soc Interface (2014)

Schematic diagram showing the E-cadherin–β-catenin dynamics as considered in the Model 1 [(a)] and Model 2 [(a) + (b)]. Free E-cadherin (E) and β-catenin (β) in the cytoplasm bind to form a complex (E/β). In adherent cells, in addition to the general transport to the cell surface, E-cadherin–β-catenin complexes are trafficked to the contact area. If the complex is transported to a site of cell–cell contact (denoted  at cell contact site i), it can bind complexes on the neighbouring cell's surface. If there is no binding partner, the complex can be internalized again and recycled. The same process takes place when bonds are broken due to junction disassembly. Whereas in Model 1, the amount of E-cadherin–β-catenin complexes that can be trafficked to one cell–cell contact site is limited, Model 2 comprises of additional dynamics such that the E-cadherin–β-catenin complexes are redistributed between contact sites when a cell has got more than one neighbouring cell as is shown in (b). (Online version in colour.)
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4305411&req=5

RSIF20141080F1: Schematic diagram showing the E-cadherin–β-catenin dynamics as considered in the Model 1 [(a)] and Model 2 [(a) + (b)]. Free E-cadherin (E) and β-catenin (β) in the cytoplasm bind to form a complex (E/β). In adherent cells, in addition to the general transport to the cell surface, E-cadherin–β-catenin complexes are trafficked to the contact area. If the complex is transported to a site of cell–cell contact (denoted at cell contact site i), it can bind complexes on the neighbouring cell's surface. If there is no binding partner, the complex can be internalized again and recycled. The same process takes place when bonds are broken due to junction disassembly. Whereas in Model 1, the amount of E-cadherin–β-catenin complexes that can be trafficked to one cell–cell contact site is limited, Model 2 comprises of additional dynamics such that the E-cadherin–β-catenin complexes are redistributed between contact sites when a cell has got more than one neighbouring cell as is shown in (b). (Online version in colour.)
Mentions: Endocytosis is followed by the disruption of the E-cadherin–β-catenin complex and the components can either be degraded, recycled for cell–cell adhesion or re-used in different signalling contexts. As production of neither E-cadherin nor β-catenin is explicitly taken into account, the possibility of degradation is also not considered in the model but it is assumed that the overall number of molecules is at a steady state. The model dynamics are shown in figure 1.Figure 1.

Bottom Line: This approach assumes that cells behave in the same biophysical manner in isolated experiments as they do within colonies and tissues.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.

View Article: PubMed Central - PubMed

Affiliation: Division of Mathematics, The University of Dundee, Dundee, UK dkschlueter@maths.dundee.ac.uk.

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.

Show MeSH
Related in: MedlinePlus