Model for biological communication in a nanofabricated cell-mimic driven by stochastic resonance

Abstract

Cells offer natural examples of highly efficient networks of nanomachines. Accordingly, both intracellular and intercellular communication mechanisms in nature are looked to as a source of inspiration and instruction for engineered nanocommunication. Harnessing biological functionality in this manner requires an interdisciplinary approach that integrates systems biology, synthetic biology, and nanofabrication. Here, we present a model system that exemplifies the synergism between these realms of research. We propose a synthetic gene network for operation in a nanofabricated cell mimic array that propagates a biomolecular signal over long distances using the phenomenon of stochastic resonance. Our system consists of a bacterial quorum sensing signal molecule, a bistable genetic switch triggered by this signal, and an array of nanofabricated cell mimic wells that contain the genetic system. An optimal level of noise in the system helps to propagate a time-varying AHL signal over long distances through the array of mimics. This noise level is determined both by the system volume and by the parameters of the genetic network. Our proposed genetically driven stochastic resonance system serves as a testbed for exploring the potential harnessing of gene expression noise to aid in the transmission of a time-varying molecular signal.

Fig. 1

Platform components for proposed system. (a) Top left: E. coli cells harboring sender constructs express the I-protein (LasI here), which catalyzes synthesis of the AHL signal 3OC12HSL. Top right: E. coli cells harboring receiver constructs express the R-protein (LasR here) which forms a complex with the AHL signal that binds and activates a quorum sensing promoter p_qsc (the rsaL promoter here). Bottom: Experimental results of a disk of sender E. coli cells activating nearby droplets of receiver cells. (b) Receiver cells function in cell-free extract (c) Cell mimic devices

Fig. 2

Proposed system for harnessing stochastic resonance. Top: Bistable genetic switch expressing both R-protein and I-protein from the quorum sensing activated p_qsc promoter. Bottom left: AHL flows into the first well of the communication channel in a time-varying fashion according to the function f(t). Bottom right: The nanofabricated communication channel is composed of individual small wells, each of which contains cell extract and the genetic network. Pores between the wells allow flow of small molecules such as the AHL signal.

Fig. 3

Demonstration of stochastic resonance. (a) AHL concentration vs. time for different array wells with no noise in the system. (b) AHL concentration vs. time for different array wells with an optimal level of noise in the system. (c) B_F(n) scores for different well volumes (μm³).

Fig. 4

Simulations demonstrating stochastic resonance with a faster input frequency w=0.01 and a) with flow of mRNA b) without flow of mRNA and c) with p decreased by a factor of 10 and k_i and k_r increased by a factor of 10 to enable resonance at larger volumes (μm³).