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Weakly Circadian Cells Improve Resynchrony

Figure 2

Mechanistic model produces diverse cells with varying response properties similar to SCN cells treated with TTX.

(A) Bioluminescence traces from cells classified as strong (left), weak (center) or arrhythmic (right) based on their amplitude in their final cycle during TTX treatment. We show the last peak before TTX treatment and then 5 cycles during treatment. (B) Simulated traces using a mechanistic model from strong, weak, and arrhythmic cells show similar oscillation qualities to the real cells. Simulated cells are classified according to their limit cycle's “cumulative amplitude”, which is the sum of peak-to-trough amplitudes of all modeled messages and proteins. (C) The range of amplitudes and phases of velocity response curves (VRCs) from strong (left) and weak (right) simulated cells; VRCs are not computable for arrhythmic simulated cells. The shaded regions indicate the areas in which model VRCs peak and trough. Two representative VRC's are shown in each plot, each with a trough and peak falling in a different place in the regions. Circadian time is defined relative to peak Per mRNA expression, which is at circadian time (CT) 7. Arrows indicate the VRC's for the cells shown in (B). By computing the area under the absolute value of the VRC, we determine each cell's ability to speed up or slow down when signaled (greater area indicates greater “shiftability”). (D) We plot the VRC area (log scale) vs. the cumulative amplitude (linear scale). Arrows indicate the data points for the example cells in (B). We include the correlation coefficient for the amplitude and natural logarithm of the VRC area. There is a negative correlation between the VRC area and the oscillatory behavior of simulated cells, indicating that weak cells are more shiftable.

Figure 2