Fig 3. S-shaped, but not ultrasensitive, responses cause a two-dimensional system of the cell cycle to oscillate.

Parameter values as indicated in the figure. (A) Block diagram of the ultrasensitive, negative feedback system (i-a). (B) Effect of relative synthesis c on the location of the [Cdk1] nullcline in the phase plane. (C) Time traces for two different initial conditions of system (i-a), denoted by either continuous or dotted line. Only one steady state exists. (D) Block diagram of the bistable, negative feedback system (i-b). (E) For wide S-shaped [APC]* nullclines, three intersections in the phase plane can exist, resulting in bistability of the overall ODE system. Closed black dots depict stable steady states, while open dots denote unstable steady states. (F) Time traces for system (i-b). Depending on the initial conditions, the system will settle in one of two stable steady states. (G) Number and position of the steady states for system (i-b). Osc = oscillations, Bi = bistable, Mono Low = one stable steady state on lower branch of [APC]* nullcline, Mono Top = one stable steady state on top branch of [APC]* nullcline. (H-I) If the [Cdk1] nullcline intersects the [APC]* nullcline in between its folds, one unstable steady state exists, resulting in oscillations.