Constructing network topologies for multiple signal-encoding functions

Cells use signaling protein networks to sense their environment and mediate specific responses. Information about environmental stress is usually encoded in the dynamics of the signaling molecules, and qualitatively distinct dynamics of the same signaling molecule can lead to dramatically different cell fates. Exploring the design principles of networks with multiple signal-encoding functions is important for understanding how distinct dynamic patterns are shaped and integrated by real cellular networks, and for building cells with targeted sensing-response functions via synthetic biology.

In this paper, we investigate multi-node enzymatic regulatory networks with three signal-encoding functions, i.e., dynamic responses of oscillation, transient activation, and sustained activation upon step stimulation by three different inducers, respectively. Taking into account competition effects of the substrates for the same enzyme in the enzymatic reactions, we searched for robust subnetworks for each signal-encoding function by three-node-network enumeration and then integrated the three subnetworks together via node-merging. The obtained tri-functional networks consisted of four to six nodes, and the core structures of these networks were hybrids of the motifs for the subfunctions.

The simplest but relatively robust tri-functional networks demonstrated that the three functions were compatible within a simple negative feedback loop. Depending on the network structure, the competition effects of the substrates for the same enzyme within the networks could promote or hamper the target functions, and can create implicit functional motifs. Overall, the networks we obtained could in principle be synthesized to construct dynamic control circuits with multiple target functions.