Combinatorial mathematical modelling approaches to interrogate rear retraction dynamics in 3D cell migration
Fig 6
The stochastic rear retraction simulator makes more plausible predictions regarding individual cell behaviour.
A. 6 stochastic simulations showing rear recoil amount with respect to time for the first 20,000s when run with exactly the same reactions and parameters as in the ODE model in Fig 3 (left) and the average of the 6 individual stochastic simulations (red line) in comparison with the previous deterministic curve (blue line) for rear retraction amount with the same parameters (right). B, 6 stochastic simulations showing the timecourse for the first 20,000s of rear retraction amounts with different substrate polarities, ranging from 0% (left) to 20% (right) of the unperturbed value. C. Average rear retraction amount of all 6 cells across the whole 20,000s for each level of perturbation of substrate stiffness polarity. D. 6 stochastic simulations showing the timecourse for the first 20,000s of rear retraction amounts with different DRF amounts, ranging from 0% (left) to 10% (right). E. Average rear retraction amount of all 6 cells across the whole 20,000s for each level of perturbation of DRF amount. F. A2780 cells were seeded in CDM, treated with DMSO (vehicle control), 5 mM, 12.5 mM or 50 mM SMIFH2 (formin inhibitor) and imaged by high-end widefield microscopy across 16 hours, representative individual cells highlighted by yellow * across t = 10 hours. G. Average speed of cells in each condition as in F shown (N = 50 cells across 3 repeats analysed per condition). **** denotes p < 0.0001 by one-way ANOVA with Tukey’s multiple comparison post-hoc test, single pooled variance. H. 6 random stochastic simulations showing the timecourse for the first 50,000s of rear retraction amount at the critical substrate stiffness polarity level (4%). I. Proportion of time of the (left): 50,000s; or (right) 1,000,000s timecourses rear recoil amount spent in the high state (defined as rear recoil > 50%), the low state (< 20%) or transitioning (trans.) between (>20%, <50%) of (left) 20 or (right) 3 simulations with substrate stiffness polarity set at 4%.