No Arabic abstract
In response to a concentration gradient of nutrient, E. coli bacterium modulates the rotational bias of flagellar motors which control its run-and-tumble motion, to migrate towards regions of high nutrient concentration. Presence of stochastic noise in the biochemical pathway of the cell has important consequence on the switching mechanism of motor bias, which in turn affects the runs and tumbles of the cell. We model the intra-cellular reaction network in terms of coupled time-evolution of three stochastic variables, kinase activity, methylation level and CheY-P protein level, and study the effect of methylation noise on the chemotactic performance of the cell. In presence of a spatially varying nutrient concentration profile, a good chemotactic performance allows the cell to climb up the concentration gradient fast and localize in the nutrient-rich regions in the long time limit. Our simulations show that the best performance is obtained at an optimal noise strength. While it is expected that chemotaxis will be weaker for very large noise, it is counter-intuitive that the performance worsens even when noise level falls below a certain value. We explain this striking result by detailed analysis of CheY-P protein level statistics for different noise strengths. We show that when the CheY-P level falls below a certain (noise-dependent) threshold, the cell tends to move down the concentration gradient of the nutrient, which has a detrimental effect on its chemotactic response. This threshold value decreases as noise is increased, and this effect is responsible for noise-induced enhancement of chemotactic performance. In a harsh chemical environment, when the nutrient degrades with time, the amount of nutrient intercepted by the cell trajectory, is an effective performance criterion. In this case also, we find an optimum noise strength, depending on the nutrient lifetime.
We show how the competition between sensing and adaptation can result in a performance peak in E.coli chemotaxis using extensive numerical simulations in a detailed theoretical model. Receptor clustering amplifies the input signal coming from ligand binding which enhances chemotactic efficiency. But large clusters also induce large fluctuations in total activity since the number of clusters go down. The activity and hence the run-tumble motility now gets controlled by methylation levels which are part of adaptation module, rather than ligand binding. This reduces chemotactic efficiency.
Two distinct mechanisms for filtering noise in an input signal are identified in a class of adaptive sensory networks. We find that the high frequency noise is filtered by the output degradation process through time-averaging; while the low frequency noise is damped by adaptation through negative feedback. Both filtering processes themselves introduce intrinsic noises, which are found to be unfiltered and can thus amount to a significant internal noise floor even without signaling. These results are applied to E. coli chemotaxis. We show unambiguously that the molecular mechanism for the Berg-Purcell time-averaging scheme is the dephosphorylation of the response regulator CheY-P, not the receptor adaptation process as previously suggested. The high frequency noise due to the stochastic ligand binding-unbinding events and the random ligand molecule diffusion is averaged by the CheY-P dephosphorylation process to a negligible level in E.coli. We identify a previously unstudied noise source caused by the random motion of the cell in a ligand gradient. We show that this random walk induced signal noise has a divergent low frequency component, which is only rendered finite by the receptor adaptation process. For gradients within the E. coli sensing range, this dominant external noise can be comparable to the significant intrinsic noise in the system. The dependence of the response and its fluctuations on the key time scales of the system are studied systematically. We show that the chemotaxis pathway may have evolved to optimize gradient sensing, strong response, and noise control in different time scales
The mean size of exponentially dividing E. coli cells cultured in different nutrient conditions is known to depend on the mean growth rate only. However, the joint fluctuations relating cell size, doubling time and individual growth rate are only starting to be characterized. Recent studies in bacteria (i) revealed the near constancy of the size extension in a single cell cycle (adder mechanism), and (ii) reported a universal trend where the spread in both size and doubling times is a linear function of the population means of these variables. Here, we combine experiments and theory and use scaling concepts to elucidate the constraints posed by the second observation on the division control mechanism and on the joint fluctuations of sizes and doubling times. We found that scaling relations based on the means both collapse size and doubling-time distributions across different conditions, and explain how the shape of their joint fluctuations deviates from the means. Our data on these joint fluctuations highlight the importance of cell individuality: single cells do not follow the dependence observed for the means between size and either growth rate or inverse doubling time. Our calculations show that these results emerge from a broad class of division control mechanisms (including the adder mechanism as a particular case) requiring a certain scaling form of the so-called division hazard rate function, which defines the probability rate of dividing as a function of measurable parameters. This gives a rationale for the universal body-size distributions observed in microbial ecosystems across many microbial species, presumably dividing with multiple mechanisms. Additionally, our experiments show a crossover between fast and slow growth in the relation between individual-cell growth rate and division time, which can be understood in terms of different regimes of genome replication control.
DNA replication is an essential process in biology and its timing must be robust so that cells can divide properly. Random fluctuations in the formation of replication starting points, called origins, and the subsequent activation of proteins lead to variations in the replication time. We analyse these stochastic properties of DNA and derive the positions of origins corresponding to the minimum replication time. We show that under some conditions the minimization of replication time leads to the grouping of origins, and relate this to experimental data in a number of species showing origin grouping.
The polarisation of cells and tissues is fundamental for tissue morphogenesis during biological development and regeneration. A deeper understanding of biological polarity pattern formation can be gained from the consideration of pattern reorganisation in response to an opposing instructive cue, which we here consider by example of experimentally inducible body axis