Applying single-cell capture technologies to studies of bacterial cell-size regulation

Under certain culture conditions, bacterial cell size can be stabilized within a certain range. Briefly, after several generations, longer cells become shorter as shorter cells become longer. This steady state phenomenon, known as cell-size homeostasis, is even observed in bacterial cells subjected to environmental fluctuations or internal noise. The scientific laws that govern cell size regulation, and the biological significance behind these laws, has long been an attractive research topic, and is one that continues today. In recent years, studies at the population level have failed to fully explain some phenomena; thus, the current trend is to explore the laws of cell-size control by following bacteria at the single-cell level. Thanks to the development of various single-cell capture technologies, it has become more feasible for researchers to carry out such research relatively easily. The results of studies of bacterial size regulation using single-cell data are inconsistent with those obtained from batch culture studies, with the former more accurately reflecting information that covers the entire population than the latter. In this review, we start by introducing bacterial single-cell capture technologies that are mainly based on long-term time-lapse microscopy. The “capture” in this context means that not only are the bacterial cells being manipulated, but that each of the traced cells is also providing phenotype information. To improve the accuracy of the results, non-destructive methods are used to minimize the impact on the growth of cells, notably by using an effective type of microfluidic chip known as the “mother machine”. Bacterial cells in the mother machine can obtain continuous fresh medium through liquid flow, allowing the observation of these living cells for long time periods. This approach is also expected to be beneficial for future downstream analysis. Next, we relate several size-control models of various bacteria: Sizer, timer, adder and noisy linear map. The sizer and timer models make sense at the population level, with each proposing that cells will divide at a specific cell size or time point, respectively. At the single-cell level, the adder and noisy linear map models offer their own explanations for maintaining cell-size homeostasis. Ultimately, all of the cells in a population get increasingly close to a specific common size over many generations. In summary, this article provides a quick overview of current trends and recent progress in bacterial cell-size regulation.