Stability of the Switch Increases Exponentially with System Size (Number of CaMKII Holoenzymes and PP1 Molecules)

<div><p>(A) Spontaneous transitions in a system with four CaMKII holoenzymes and four PP1 enzymes. Phosphorylation fraction is <i>Sp_tot</i>/12<i>N_CaMK</i>.</p> <p>(B) System with 16 holoenzymes and 16 PP1 enzymes, with four times the volume of (A). Note different timescales between (A) and (B). Phosphorylation fraction is <i>Sp_tot</i>/12<i>N_CaMK</i>.</p> <p>(C) The switch's lifetime increases exponentially with system size. Numbers of all species scale together with system volume. Circles are data points, line is a linear fit, indicating an exponential dependence, because the ordinate is in logarithmic scale. The red asterisks indicate data points where we included the PP1–I1P fluctuations explicitly.</p>