Figure 6
Circuit dynamics driven by the Grb2 and Gab1 signals shown in the Rac1/RhoA phase plane diagram.
(a) The Grb2 signal increase from 0 to 1.0 × 106 molecules (Gab1 = 0). Initially, the system is tristable (cells can be in either A, M or A/M phenotype). Next, Grb2 is gradually increased, during which we calculated a sequence of the stable states (The red dots that extend from the initial green stable states) and the saddle points among them (The blue dots that extend from the initial saddle points). In other words, the figure shows several superimposed phase plane diagrams for the cases of different Grb2 levels. When Grb2 is gradually increased, the A phenotype disappears first – the red and the blue dots come close and eventually disappear, implying that the cell loses the potential to be A phenotype. Upon further increase of Grb2, the A/M phenotype also disappears. It means that for high Grb2 input the cells can only be in the mesenchymal phenotype (See Supplementary Movie S1). (b) Similar to (a) but for an increase in Gab1 input from 0 to 3.0 × 105 molecules (Grb2 = 0). In this case, the A/M phenotype is the first to disappear and then the mesenchymal phenotype. It means that for high Gab1 input the cells can only be in the amoeboid phenotype (See Supplementary Movie S2). The gradients of both red and blue from light to dark represent the temporal increase of Grb2 and Gab1 signals. The black arrows indicate the direction in which each state moves as the signal increases.
