Fig. 4.

Fold-change response has higher information transduction capacity. (A) Noisy, overlapping response distributions provide low information about the strength of ligand input. (B and C) To compute the maximum mutual information, we stimulated the cells with different doses of Tgf-β1 (Fig. 3). The response distributions for three doses are shown here, of the absolute fluorescence level (B) or the fold change (C). (Bottom) Overlay of the distributions. For low, medium, and high doses, the number of cells examined was 277, 290, and 532, respectively. (D) We computed the maximum mutual information between ligand input and different features of the nuclear NG-Smad3 response. Features computed using the absolute response are shown in orange, and features computed using the fold-change response are shown in blue. Level and fold change of nuclear NG-Smad3 were evaluated at steady state, at 36 min after Tgf-β addition (comparison at different time points is shown in Fig. S5B). Rate of change in the NG-Smad3 response was computed as the maximum of the derivative of the response curve. To compute the integral of the NG-Smad3 response, the response was integrated over the first hour of ligand stimulation. For dynamic measurements, the level of nuclear NG-Smad3 was measured at multiple time points, as indicated, and mutual information was computed with a 2D distribution (Fig. S8). Error bars are 90% confidence intervals computed using bootstrap resampling. The total number of cells examined for each calculation was 1,650.