Robust network topologies for generating switch-like cellular responses.

摘要: Signaling networks that convert graded stimuli into binary, all-or-none cellular responses are critical in processes ranging from cell-cycle control to lineage commitment. To exhaustively enumerate topologies exhibit this switch-like behavior, we simulated all possible two- and three-component on random parameter sets, assessed the resulting response profiles for both steepness (ultrasensitivity) extent of memory (bistability). Simulations were used study purely enzymatic networks, transcriptional hybrid enzymatic/transcriptional each class rank ordered by parametric robustness (i.e., percentage applied sets exhibiting ultrasensitivity or bistability). Results reveal distribution network is highly skewed, with most robust clustering a small number motifs. Hybrid generating (up 28%) bistability 18%); strikingly, framework fragile either ultrasensitive 3%) bistable 1%) responses. The disparity among classes due part zero-order ultrasensitivity, an enzyme-specific phenomenon, which repeatedly emerges as particularly mechanism nonlinearity can act building block We also highlight experimentally studied examples enabling switching native synthetic systems, our simulations. This unbiased approach identifying capable given may be useful discovering new natural motifs designing gene networks.