Synthetic gene circuits that can precisely program cellular behavior have enormous potential for applications in engineering and medicine. However, constructing synthetic gene circuits with reliable, non-trivial function is extremely difficult. A major challenge is to deal with cellular ‘noise' or the stochastic variability in gene expression, which is a consequence of small numbers of interacting molecules. Noise poses a significant challenge for individual cells to carry out reliable function in the presence of such unreliable gene expression. Nevertheless, nature is amazingly successful in achieving robust function despite cellular noise.

Past efforts to understand the mechanisms underlying the regulation of gene expression have focused on the role of feedback and feedforward control. Our work focuses on an alternative mechanism: cell-cell communication. In particular, we analyze quorum sensing, a mechanism by which cells broadcast and sense their population density through diffusible signaling molecules. At sufficiently high concentrations, these signaling molecules activate downstream genes with diverse physiological functions.

Using computer simulations, we show that the diffusion of the signaling molecule across the cell membrane can effectively regulate noise in the signaling molecule. At low diffusion rates, the signaling molecules are trapped inside the cell and fluctuations are prevalent. On the other hand, at high diffusion rates, coupling with the external pool of the molecule can effectively absorb or “buffer” these fluctuations. Further downstream, the signaling molecule binds to a protein to form a complex from which dimers are then formed. The kinetic rates of the complex formation and dimerization processes also have an impact on noise. With slower kinetic rates, the noise increases and the maximum efficacy of noise reduction is observed in a smaller range of diffusion rates.

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