A central question in cell biology is how cells regulate their growth and division. Our group’s research has also focused on this question by using mathematical modeling to make testable predictions and compare them to existing experimental data. The typical experimental data that are often used in these studies are obtained from a microfluidic device called a “mother-machine.” Cells under study, such as Escherichia coli in our case, are made to flow into these channels, where they grow and their lengths are tracked. The question that arises is why is cell length, but not other cell characteristics such as cell volume, tracked? In fact, it makes sense to track cell volume because the biochemical reactions controlling growth and division depend on the concentration of protein species involved in these cellular processes. Because concentration is inversely proportional to cell volume, it should be the relevant quantity of interest. However, previous studies have assumed cell volume and cell length to be equivalent measures for rod-shaped bacteria such as E. coli.

While we were writing a grant on cell cycle modeling, we wanted to justify the use of cell length data from mother-machine experiments. Some studies measured cell width variability in E. coli and found it to be small, thus providing reasoning for cell volume and cell length to be equivalent measures in E. coli.  However, we found no explicit study that tested that. Surprisingly, a previous study by Facchetti et al. in Biophysical Journal reported the opposite in rod-shaped fission yeast. Cell cycle analyses based on cell length gave qualitatively different results compared to those based on surface area or volume, even when cell width variability was small. We sought to answer in our paper if that is the case in E. coli. Our image on the cover of the May 6 issue of Biophysical Journal is also inspired by this question on single-cell measurements in which we show an artistic rendition of cells with measuring tapes around them.

We found that cell length and cell volume are indeed interchangeable characteristics for cell cycle studies. We also discovered that most of the measured cell width variability in previous studies of E. coli is dominated by measurement noise. Our study justifies the use of cell length as an appropriate proxy for cell surface area or cell volume in cell cycle studies of E. coli.

— Prathitha Kar and Ariel Amir