Multiple timescales in bacterial growth homeostasis

In balanced exponential growth, bacteria maintain many properties statistically stable for a long time: cell size, cell cycle time, and more. As these are strongly coupled variables, it is not a-priori obvious which are directly regulated and which are stabilized through interactions. Here, we address this problem by separating timescales in bacterial single-cell dynamics. Disentangling homeostatic set points from fluctuations around them reveals that some variables, such as growth-rate, cell size and cycle time, are sloppywith highly volatile set points. Quantifying the relative contribution of environmental and internal sources, we find that sloppiness is primarily driven by the environment. Other variables such as fold-change define stiffcombinations of coupled variables with robust set points. These results are manifested geometrically as a control manifold in the space of variables: set points span a wide range of values within the manifold, whereas out-of -manifold deviations are constrained. Our work offers a generalizable data-driven approach for identifying control variables in a multidimensional system.

Automated summary

In balanced exponential growth, some variables in bacterial single-cell dynamics are sloppily regulated while others define stiff combinations with robust set points. Sloppiness is primarily driven by the environment, while set points of stiff combinations span a wide range of values within the manifold.