Comparative analysis for noise propagation in a coarse-grained model linking metabolism to cellular growth

Fluctuations in growth rate have been shown to be important drivers of phenotypic heterogeneity. So far they have been usually related to gene expression or enzymatic reactions, since the metabolism was supposed to average the mixture of many and different noisy reactions involved in it. On the other hand, single-cell experiments have recently highlighted how noise may well propagate also from metabolic reactions, and influence cellular growth rate. In this work, a coarse-grained model of the relationships linking cellular resources to growth rate and metabolism is investigated with respect to noise propagation. An incoherent feedforward control is exerted by growth rate on metabolic enzymes, since growth is supposed to positively control both metabolic enzymes production and degradation. Different noise sources have been addressed, affecting metabolic production, cellular resource clearance and production. Noise sources have been addressed one at a time, and noise propagation has been investigated by means of a Stochastic Hybrid System model, whose shape is modulated according to the different noise sources. Results provide interesting biological insights about the causal relationship concerning noise propagation from growth to metabolism and vice versa.