Research ArticleCELL BIOLOGY

Concurrent processes set E. coli cell division

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Science Advances  07 Nov 2018:
Vol. 4, no. 11, eaau3324
DOI: 10.1126/sciadv.aau3324

Figures

  • Fig. 1 The concurrent processes hypothesis.

    (A) Explanation of the replication-related cell cycle intervals in E. coli. Replication initiation occurs after a B period, followed by the C (replication) and D (termination to division) periods, and the B and C + D periods can be measured in single cells by proxies of replication initiation (6, 12). (B) Classically, replication-segregation is believed to be rate limiting for cell division; a recent hypothesis by Harris and Theriot (8) states that the rate-limiting process might be instead the formation of the septum. (C) Our concurrent processes hypothesis states that cell division is the result of the slowest between a cell-related interdivision process (setting division when, e.g., the septum machinery is ready) and a chromosome-related process (setting division when replication-segregation is complete). Hence, the circuit is analogous to an AND gate. (D) Scheme of the mathematical model.

  • Fig. 2 A concurrent processes model explains the correlation patterns for the C + D period.

    (A) and (B) plot the unexplained patterns for the C + D period. (A) Cell growth during the C + D period, quantified by the logarithmic ratio between the final and initial volume (y axis, binned averages), anticorrelates with cell size at initiation (x axis). The plot is centered by the mean values of the x- and y-axis variables to compare different datasets. Solid lines are linear fits. (B) The duration of the C + D period (y axis, binned averages) anticorrelates with the growth rate of individual cells (x axis), with a near-inverse pattern. (C) The correlation between size at initiation and growth during the C + D period (A) attains the observed intermediate slopes (gray shaded area) in the concurrent processes hypothesis (cyan lines; see Materials and methods for parameters), but not if one assumes that replication is always (orange line) or never limiting (purple line) cell division. Solid lines correspond to theoretical predictions, and the shaded area to the range of slopes allowed by the plots in (A). (D) The anticorrelation between C + D period duration and growth rate of individual cells (B) is absent if replication is always bottleneck (orange line). Instead, the concurrent processes hypothesis captures experimental trends quantitatively [cyan lines have the same parameters as in (B); see Materials and methods]. Solid lines correspond to theoretical predictions. Data are from (6, 12).

  • Fig. 3 Predictions of the concurrent processes model beyond the C + D period are verified in data.

    (A) In the data, growth quantified by logarithmic final to initial size ratio in the C + D period has a weak negative correlation with growth in the B period [see (18)]. (B) This correlation falls in the range where the replication and interdivision processes compete to set cell division (cyan lines; obtained with the same parameters as in Fig. 2, B and D, listed in Materials and methods). (C and D) The negative correlation of interdivision time with individual cell growth rate [exemplified for one dataset in (C)] has a decreasing trend with increasing growth rate, captured by the model (cyan line; pH = 0.25; other parameters were fixed as in the other figures; see Materials and methods). Cell cycle subperiod data are from (6, 12). Interdivision cycle data [in (D)] are from (6, 10, 19, 28).

  • Fig. 4 Parameter definitions and illustration of the concurrent processes model.

    (A) Definition of size variables and control parameters used in the model. (B) Implementation of the concurrent process model. Schematic (top) and algorithm (bottom). In the cell process (purple), Embedded Image sets a desired final size Embedded Image, while in the chromosome process (orange), the initiation size Embedded Image sets both the initiation size Embedded Image and a desired final size Embedded Image. To set the actual final size Embedded Image (blue), the cell and chromosome process compete through Embedded Image and Embedded Image, and the largest desired size (or, equivalently, the slowest process) sets cell division. Once the division size of cycle i, and hence the size at birth of the cycle i + 1, is set, new size-coupled stochastic division and initiation events are programmed for the next cell cycle.

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