Adaptive tuning of cell sensory diversity without changes in gene expression

Abstract

In the face of uncertainty, cell populations tend to diversify to enhance survival and growth. Previous studies established that cells can optimize such bet hedging upon environmental change by modulating gene expression to adapt both the average and diversity of phenotypes. Here, we demonstrate that cells can tune phenotypic diversity also using posttranslational modifications. In the chemotaxis network of Escherichia coli, we find, for both major chemoreceptors Tar and Tsr, that cell-to-cell variation in response sensitivity is dynamically modulated depending on the presence or absence of their cognate chemoeffector ligands in the environment. Combining experiments with mathematical modeling, we show that this diversity tuning requires only the environment-dependent covalent modification of chemoreceptors and a standing cell-to-cell variation in their allosteric coupling. Thus, when environmental cues are unavailable, phenotypic diversity enhances the population’s readiness for many signals. However, once a signal is perceived, the population focuses on tracking that signal.

E. colichemotaxis is information-limited

“…The strain used for the FRET experiments is a derivative of E. coli K-12 strain RP437 (HCB33), a gift of T. Shimizu, and described in detail elsewhere 18,34 . In brief, the FRET acceptor-donor pair (CheY-mRFP and CheZ-mYFP) is expressed in tandem from plasmid pSJAB106 18 under an isopropyl β-D-thiogalactopyranoside (IPTG)-inducible promoter.…”

“…Single-cell FRET microscopy and cell culture was carried out essentially as described previously 18,34 . In brief, cells were picked from a frozen stock at −80°C and inoculated in 2 mL of Tryptone Broth (TB; 1% bacto tryptone, 0.5 % NaCl) and grown overnight to saturation at 30°C and shaken at 250 RPM.…”

“…Microfluidic devices for the FRET experiments 34 were constructed from polydimethylsiloxane (PDMS) on 24 x 60 mm cover glasses (#1.5) following standard soft lithography protocols 47 . Briefly, the master molds for the device were created with a negative SU-8 photoresist on 100-mm silicon wafers.…”

“…Having quantified the input statistics, we turned to measuring the response and noise properties of CheA kinase activity (SI) using Förster resonance energy transfer (FRET) between the kinase’s substrate CheY and the phosphatase CheZ inside single cells 17,18,34 (Fig. 2B).…”

“…In this regime, the response is fully characterized by how it amplifies different frequencies in the signal, K ( ω ), or equivalently, the response to an impulse (delta function) of signal, K ( t ). To measure the impulse response K ( t )to MeAsp, we used a microfluidic device that allows us to rapidly switch (in ∼100 ms) the concentration of attractant delivered to hundreds of immobilized cells 34 (Figs. S3).…”