RT Journal Article SR Electronic T1 Multiple timescales in bacterial growth homeostasis JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.03.30.437502 DO 10.1101/2021.03.30.437502 A1 Alejandro Stawsky A1 Harsh Vashistha A1 Hanna Salman A1 Naama Brenner YR 2021 UL http://biorxiv.org/content/early/2021/03/31/2021.03.30.437502.abstract AB Microbial growth and division are fundamental processes relevant to many areas of life science. Of particular interest are homeostasis mechanisms, which buffer growth and division from accumulating random fluctuations. This classic problem has seen recent advance in both theory and experiments, but still much remains unclear and debatable. Because there are many coupled processes inside the cell, it is not a-priori clear which variables are under regulation and which are stabilized by their coupling to regulated variables. Here, we address this question by distentangling homeostatic set-points – estimated as temporal averages across individual lineages – from fluctuations around them. Applying variance decomposition to individually trapped bacteria (mother machine data), we find that phenotypic variables estimated from cell-size measurements (inter-division time, growth rate, added size and more), exhibit a range of different behaviors. Some have flexible set-points that vary significantly between lineages - “sloppy” variables, while others are tightly fixed - “stiff” variables. Analyzing pairs of trapped lineages (sisters machine data), reveals that the primary source of sloppiness is a high sensitivity to the trap environment, while lineage-specific factors contribute only a small fraction. We find strong long-term correlations between sloppy set-points, and identify a control manifold in the space of growth and division variables. Cell size is also a sloppy variable, however its set-point is uncoupled to growth variables; such correlations appear only on the short, single-cycle timescale. We discuss these results in light of recent models of cell size control, and point to new avenues of research.Competing Interest StatementThe authors have declared no competing interest.