Table 3 Setups of the four main simulations referred to in the main figures.
From: Computational evidence for multi-layer crosstalk between the cadherin-11 and PDGFR pathways
Name | Explanation | Parameters changed |
|---|---|---|
Baseline model | All interactions are active in the network. We use the parameters in Table 2 without alterations | |
Cadherin-11 knockdown | We mimic the cadherin-11 knockdown by setting the initial cell–cell contact to 0. This way cadherin-11 can never be present during the simulation, similar to an experimental knockdown of the protein4 | \(c=0\) |
Cell–cell contact off and cadherin–PDGFR-α binding off | Mimicking the Madarampalli et al., 2019 experiments, cadherin-11 is not able to bind to another cadherin-11 or PDGFR-α. Since it cannot dimerize with another cadherin-11, it cannot inhibit β-catenin, but it can bind to PDGFR-β via intermembrane domains and inhibit its activity, suggesting that this binding is not via an extracellular site but via intermembrane sites of the two receptors | \(c=0\) \({\beta }_{Bca{t}_{b{y}_{cdh11}}}\)= 0 \(cdh11=0.18\) |
Cell–cell contact off and cadherin–PDGFR-β binding off | Mimicking the Madarampalli et al., 2019 experiments, interaction of cadherin-11 and PDGFR-β on the cell membrane is blocked, cadherin-11 binding to PDGFR-α is still possible | \({\alpha }_{cdh{11}_{b{y}_{c}}}=0\) |
Crosstalk disabled | We disable the activation of PDGFR-α by cadherin-11, inhibition of PDGFR-β by cadherin-11, and inhibition of DUSP1 by β-catenin | \({\alpha }_{{pdgfrA}_{{by}_{c}}}=0\) \({\beta }_{pdgf{rB}_{b{y}_{cdh11}}}=0\) \({\beta }_{{dusp1}_{b{y}_{Bcat}}}=0\) |
Crosstalk disabled and cadherin-11 knockdown | In addition to the changes in the “crosstalk disabled” simulation, we set cell–cell contact to 0 | \({\alpha }_{{pdgfrA}_{{by}_{c}}}=0\) \({\beta }_{pdgf{rB}_{b{y}_{cdh11}}}=0\) \({\beta }_{{dusp1}_{b{y}_{Bcat}}}=0\) \(c=0\) |
Receptor interaction disabled | Crosstalk disabled only at the receptor level by blocking the activation and inhibition of PDGFR-α and PDGFR-β by cadherin-11 | \({\alpha }_{{pdgfrA}_{{by}_{c}}}=0\) \({\beta }_{pdgf{rB}_{b{y}_{cdh11}}}=0\) |
Receptor interaction disabled and cadherin-11 knockdown | In addition to the changes in the “receptor interaction disabled” simulation, we set the cell–cell contact to 0 | \({\alpha }_{{pdgfrA}_{{by}_{c}}}=0\) \({\beta }_{pdgf{rB}_{b{y}_{cdh11}}}=0\) \(c=0\) |
Downstream interaction disabled | Crosstalk disabled only at the level of β-catenin inhibiting DUSP1, while receptor level crosstalk is active | \({\beta }_{{dusp1}_{b{y}_{Bcat}}}=0\) |
Downstream interaction disabled and cadherin-11 knockdown | Crosstalk disabled at the level of β-catenin inhibiting DUSP1 and cell–cell contact set to 0 | \({\beta }_{{dusp1}_{b{y}_{Bcat}}}=0\) \(c=0\) |
