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Modular Design of Artificial Tissue Homeostasis: Robust Control through Synthetic Cellular Heterogeneity

Figure 4

Systems 3 and 4.

(A) Circuit diagram for System 3: in addition to System 2 modules, the AND gate integrates the output of the oscillator (red module) that allows commitment only when peaking. (B) Time trajectories for a simulation starting with a small stem cell population. The oscillator activator () is plotted for some representative stem cells (right axis, a.u.). (C) Individual rows track the single-cell UPC module output (, shown as a heat map) in uncommitted cells within a population. White signifies single-cell commitment, followed by black “null space” that is filled by newly divided uncommitted cells. Due to the oscillator, only a fraction of the cells commit when the concentration is high. (D) Overall system performance, S/N, as a function of the module time-scale for cell communication, . Several hundred different sets of time-scales were tested, with all time-scale parameters simultaneously varied. Each point represents an individual set of time-scales. Color and contour lines indicate point density. (E) Circuit diagram for System 4: a throttle mechanism (red module) activates during a cell's commitment and represses commitment in its neighbors. (F–G) Time trajectories for a simulation starting with a small stem cell population, where B shows the average throttle signaling component () in the external medium (right axis, a.u.) over time. (H) S/N as a function of the module time-scale for cell communication, .

doi: https://doi.org/10.1371/journal.pcbi.1002579.g004