Multiple timescales in bacterial growth homeostasis

Alejandro Stawsky; Harsh Vashistha; Hanna Salman; Naama Brenner

doi:10.1016/j.isci.2021.103678

Multiple timescales in bacterial growth homeostasis

iScience. 2021 Dec 28;25(2):103678. doi: 10.1016/j.isci.2021.103678. eCollection 2022 Feb 18.

Authors

Alejandro Stawsky^{1

2}, Harsh Vashistha³, Hanna Salman³, Naama Brenner^{2

4}

Affiliations

¹ Interdisciplinary Program in Applied Mathematics, Technion, Haifa, Israel.
² Network Biology Research Laboratories, Technion, Haifa, Israel.
³ Department of Physics and Astronomy, University of Pittsburgh, Pittsburgh, PA 15260, USA.
⁴ Department of Chemical Engineering, Technion, Haifa, Israel.

Abstract

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 "sloppy" with 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 "stiff" combinations 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.

Keywords: Microbiology; Systems biology.