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Single-Cell Biophysics: Measurement, Modulation, and Modeling
Sunday Speaker Abstracts
24
Interrogating the Bacterial Cell Cycle by Cell Dimension Perturbations and Stochastic
Modeling
Hai Zheng
1,2
,
Po-Yi Ho
3
, Meiling Jiang
1
, Bin Tang
4
, Weirong Liu
1,2
, Dengjin Li
1
, Xuefeng Yu
5
,
Nancy Kleckner
6
, Ariel Amir
3
, Chenli Liu
1,2
.
3
Harvard University, Cambridge, MA, USA,
1
Shenzhen Institutes of Advanced Technology,
Shenzhen, China,
2
University of Chinese Academy of Sciences, Beijing, China,
4
Southern
University of Science and Technology, Shenzhen, China,
5
Shenzhen Institutes of Advanced
Technology, Shenzhen, China,
6
Harvard University, Cambridge, MA, USA.
Bacteria tightly regulate and coordinate the various events in their cell cycles to duplicate
themselves accurately and to control their cell sizes. Growth of
Escherichia coli
, in particular,
follows Schaechter’s growth law. The law says that average cell volume scales exponentially
with growth rate, with a scaling exponent equal to the time from initiation of a round of DNA
replication to the cell division at which the corresponding sister chromosomes segregate. Here,
we test the robustness of the growth law to systematic perturbations in cell dimensions achieved
by varying the expression levels of mreB and ftsZ. We found that decreased mreB levels resulted
in increased cell width, with little change in cell length, whereas decreased ftsZ levels resulted in
increased cell length. In both cases, the time from replication termination to cell division
increased with the perturbed dimension. Importantly, the growth law remained valid over a range
of growth conditions and dimension perturbations. The growth law can be quantitatively
interpreted as a consequence of a tight coupling of cell division to replication initiation. Its
robustness to perturbations in cell dimensions strongly supports models in which the timing of
replication initiation governs that of cell division, and cell volume is the key phenomenological
variable governing the timing of replication initiation. These conclusions are discussed in the
context of our recently proposed “adder-per-origin” model, in which cells add a constant volume
per origin between initiations and divide a constant time after initiation.