Figure 1.
(A) The synthesis and degradation of cyclin proteins is regulated by transcription factors (TFE and TFB) and by ubiquitination machinery (SCF, Cdc20 and Cdh1). (B) Three successive cell cycles are simulated as explained in the Methods. Upper panel: gray curve, 30·M(t); blue curve, [CycE]·M(t); the gold line and the pink line indicate the time periods when TFE = 1 and SCF = 1, respectively. Lower panel: green curve, [CycA]·M(t); red curve, [CycB]·M(t); the colored bars indicate the time periods when the Boolean variables are active, according to the legend in the inset.
Table 1.
Hybrid model of mammalian cell cycle control.
Figure 2.
(A,C,E) Flow cytometry data from Yan et al [42]. DNA = 190 corresponds to G1 and DNA = 380 corresponds to G2/M. (B,D,F) Our simulations. We are plotting the total amount of cyclin A and cyclin B per cell, i.e., [CycA]·M(t) and [CycB]·M(t). DNA = 1 in G0/G1 phase; = 2 in G2/M phase. Some ‘instrumental noise’ has been added to the calculated levels of cyclins and DNA, as described in the Methods. The arrows in (A, B) indicate the rate of cyclin B accumulation in S phase in the measurements and in the model. The arrows in (C, D) indicate the cyclin A level at the onset of DNA synthesis, compared to the maximum expression level of ∼600 AU.
Figure 3.
Model predictions of cyclin E dynamics.
(A) Scatter plots. (B) Stochastic limit cycle in the state space of cyclins A, B and E. We provide two different perspectives of this three dimensional figure to help visualize how the cyclin levels go up and down. In addition, we have added golden-colored balls to help guide the eye along the cell cycle trajectory. Each ball represents the average of the cyclin levels of all the cells binned over a hundredth of the φi interval [0,1], where φi refers to the fraction of the cell cycle completed by cell i (as described in the Methods section). Finally, it may help to recognize that Fig. 2E is a projection of the data on the CycA-CycB plane, and Fig. 3B is a projection on the CycA-CycE plane.
Figure 4.
Contact inhibition of a culture of human umbilical vein endothelial cells.
(A) Growth curve for the HUVEC population over 10 days, showing the base-10 logarithm of the cell count for both experimental data and our simulation (with N0 = 11000 and N1 = 500). (B) Daily distribution of cells across the phases of the cell cycle, from experimental data. (C) Model simulation of the phase distributions.