Optimal receptor-cluster size determined by intrinsic and extrinsic noise

Biological cells sense external chemical stimuli in their environment using cell-surface receptors. To increase the sensitivity of sensing, receptors often cluster. This process occurs most noticeably in bacterial chemotaxis, a paradigm for sensing and signaling in general. While amplification of weak stimuli is useful in the absence of noise, its usefulness is less clear in the presence of extrinsic input noise and intrinsic signaling noise. Here, exemplified in a bacterial chemotaxis system, we combine the allosteric Monod-Wyman-Changeux model for signal amplification by receptor complexes with calculations of noise to study their interconnectedness. Importantly, we calculate the signal-to-noise ratio, describing the balance of beneficial and detrimental effects of clustering for the cell. Interestingly, we find that there is no advantage for the cell to build receptor complexes for noisy input stimuli in the absence of intrinsic signaling noise. However, with intrinsic noise, an optimal complex size arises in line with estimates of the size of chemoreceptor complexes in bacteria and protein aggregates in lipid rafts of eukaryotic cells.