49 research outputs found
Limits of feedback control in bacterial chemotaxis
Inputs to signaling pathways can have complex statistics that depend on the
environment and on the behavioral response to previous stimuli. Such behavioral
feedback is particularly important in navigation. Successful navigation relies
on proper coupling between sensors, which gather information during motion, and
actuators, which control behavior. Because reorientation conditions future
inputs, behavioral feedback can place sensors and actuators in an operational
regime different from the resting state. How then can organisms maintain proper
information transfer through the pathway while navigating diverse environments?
In bacterial chemotaxis, robust performance is often attributed to the zero
integral feedback control of the sensor, which guarantees that activity returns
to resting state when the input remains constant. While this property provides
sensitivity over a wide range of signal intensities, it remains unclear how
other parameters affect chemotactic performance, especially when considering
that the swimming behavior of the cell determines the input signal. Using
analytical models and simulations that incorporate recent experimental
evidences about behavioral feedback and flagellar motor adaptation we identify
an operational regime of the pathway that maximizes drift velocity for various
environments and sensor adaptation rates. This optimal regime is outside the
dynamic range of the motor response, but maximizes the contrast between run
duration up and down gradients. In steep gradients, the feedback from
chemotactic drift can push the system through a bifurcation. This creates a
non-chemotactic state that traps cells unless the motor is allowed to adapt.
Although motor adaptation helps, we find that as the strength of the feedback
increases individual phenotypes cannot maintain the optimal operational regime
in all environments, suggesting that diversity could be beneficial.Comment: Corrected one typo. First two authors contributed equally. Notably,
there were various typos in the values of the parameters in the model of
motor adaptation. The results remain unchange
Adaptation dynamics in densely clustered chemoreceptors
In many sensory systems, transmembrane receptors are spatially organized in
large clusters. Such arrangement may facilitate signal amplification and the
integration of multiple stimuli. However, this organization likely also affects
the kinetics of signaling since the cytoplasmic enzymes that modulate the
activity of the receptors must localize to the cluster prior to receptor
modification. Here we examine how these spatial considerations shape signaling
dynamics at rest and in response to stimuli. As a model, we use the chemotaxis
pathway of Escherichia coli, a canonical system for the study of how organisms
sense, respond, and adapt to environmental stimuli. In bacterial chemotaxis,
adaptation is mediated by two enzymes that localize to the clustered receptors
and modulate their activity through methylation-demethylation. Using a novel
stochastic simulation, we show that distributive receptor methylation is
necessary for successful adaptation to stimulus and also leads to large
fluctuations in receptor activity in the steady state. These fluctuations arise
from noise in the number of localized enzymes combined with saturated
modification kinetics between localized enzymes and receptor substrate. An
analytical model explains how saturated enzyme kinetics and large fluctuations
can coexist with an adapted state robust to variation in the expression level
of the pathway constituents, a key requirement to ensure the functionality of
individual cells within a population. This contrasts with the well-mixed
covalent modification system studied by Goldbeter and Koshland in which mean
activity becomes ultrasensitive to protein abundances when the enzymes operate
at saturation. Large fluctuations in receptor activity have been quantified
experimentally. Here we clarify their mechanistic relationship with
well-studied aspects of the chemotaxis system, precise adaptation and
functional robustness.Comment: Pontius W, Sneddon MW, Emonet T (2013) Adaptation Dynamics in Densely
Clustered Chemoreceptors. PLoS Comput Biol 9(9): e1003230.
doi:10.1371/journal.pcbi.100323
Recommended from our members
Hidden Stochastic Nature of a Single Bacterial Motor
The rotary flagellar motor of Escherichia coli bacterium switches stochastically between the clockwise (CW) and counterclockwise (CCW) direction. We found that the CW and CCW intervals could be described by a gamma distribution, suggesting the existence of hidden Markov steps preceding each motor switch. Power spectra of time series of switching events exhibited a peaking frequency instead of the Lorentzian profile expected from standard kinetic two-state models. Our analysis indicates that the number of hidden steps may be a key dynamical parameter underlying the switching process in a single bacterial motor as well as in large cooperative molecular systems.Molecular and Cellular BiologyPhysic
Recommended from our members
Fine-Tuning of Chemotactic Response in E. coli Determined by High-Throughput Capillary Assay
In E. coli, chemotactic behavior exhibits perfect adaptation that is robust to changes in the intracellular concentration of the chemotactic proteins, such as CheR and CheB. However, the robustness of the perfect adaptation does not explicitly imply a robust chemotactic response. Previous studies on the robustness of the chemotactic response relied on swarming assays, which can be confounded by processes besides chemotaxis, such as cellular growth and depletion of nutrients. Here, using a high-throughput capillary assay that eliminates the effects of growth, we experimentally studied how the chemotactic response depends on the relative concentration of the chemotactic proteins. We simultaneously measured both the chemotactic response of E. coli cells to l-aspartate and the concentrations of YFP-CheR and CheB-CFP fusion proteins. We found that the chemotactic response is fine-tuned to a specific ratio of [CheR]/[CheB] with a maximum response comparable to the chemotactic response of wild-type behavior. In contrast to adaptation in chemotaxis, that is robust and exact, capillary assays revealed that the chemotactic response in swimming bacteria is fined-tuned to wild-type level of the [CheR]/[CheB] ratio.Molecular and Cellular Biolog
Single-cell quantification of IL-2 response by effector and regulatory T cells reveals critical plasticity in immune response
The sensitivity of T cells to interleukin-2 (IL-2) can vary by three orders of magnitude and is determined by the surface densities of the IL-2 receptor α subunits.Regulatory T cells inflict a double hit on effector T cells by lowering the bulk IL-2 concentration as well as the sensitivity of effector T cells to this crucial cytokine.This double hit deprives weakly activated effector T cells of pSTAT5 survival signals while having only minimal effects on strongly activated effector cells that express increased levels of the IL-2 receptor.Short-term signaling differences lead to a differential functional in terms of proliferation and cell division: regulatory T cell specifically suppress weakly activated effector T cells even at large numbers; small numbers of strongly activated effector T cells overcome the suppression
Minimally invasive determination of mRNA concentration in single living bacteria
Fluorescence correlation spectroscopy (FCS) has permitted the characterization of high concentrations of noncoding RNAs in a single living bacterium. Here, we extend the use of FCS to low concentrations of coding RNAs in single living cells. We genetically fuse a red fluorescent protein (RFP) gene and two binding sites for an RNA-binding protein, whose translated product is the RFP protein alone. Using this construct, we determine in single cells both the absolute [mRNA] concentration and the associated [RFP] expressed from an inducible plasmid. We find that the FCS method allows us to reliably monitor in real-time [mRNA] down to ∼40 nM (i.e. approximately two transcripts per volume of detection). To validate these measurements, we show that [mRNA] is proportional to the associated expression of the RFP protein. This FCS-based technique establishes a framework for minimally invasive measurements of mRNA concentration in individual living bacteria
Vignette detection and reconstruction of composed ornaments with a strengthened autoencoder
A strengthened autoencoder formed by placing an object detector upstream of a decoder is here developed in the context of the model-helped human analysis of composed ornaments from a dictionary of vignettes. The detection part is in charge to detect regions of interest containing some vignette features, and the decoding part to ensure vignette reconstruction with a relative quality depending on feature match. Images of ornaments without typographical composition are generated in order to properly assess the performance of each of the two parts
Non-Genetic Diversity in Chemosensing and Chemotactic Behavior
Non-genetic phenotypic diversity plays a significant role in the chemotactic behavior of bacteria, influencing how populations sense and respond to chemical stimuli. First, we review the molecular mechanisms that generate phenotypic diversity in bacterial chemotaxis. Next, we discuss the functional consequences of phenotypic diversity for the chemosensing and chemotactic performance of single cells and populations. Finally, we discuss mechanisms that modulate the amount of phenotypic diversity in chemosensory parameters in response to changes in the environment
E. coli chemotaxis is information-limited
Organisms must acquire and use environmental information to guide their
behaviors. However, it is unclear whether and how information quantitatively
limits behavioral performance. Here, we relate information to behavioral
performance in Escherichia coli chemotaxis. First, we derive a theoretical
limit for the maximum achievable gradient-climbing speed given a cell's
information acquisition rate. Next, we measure cells' gradient-climbing speeds
and the rate of information acquisition by the chemotaxis pathway. We find that
E. coli make behavioral decisions with much less than the 1 bit required to
determine whether they are swimming up-gradient. However, they use this
information efficiently, performing near the theoretical limit. Thus,
information can limit organisms' performance, and sensory-motor pathways may
have evolved to efficiently use information from the environment.Comment: 17 pages of main text, 3 main text figures, 66 pages of supplementary
text, 10 supplementary figure