单细菌捕获技术应用于细菌尺寸调控规律

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

在规定的培养条件下,细菌的细胞尺寸大小能稳定在一定的范围内,即便遭受环境波动或自身内部噪声影响,细菌细胞仍能够维持自身尺寸稳态.这种尺寸调控遵循怎样的规律,以及规律背后的生物学意义如何,一直以来都吸引着人们关注,相关研究也在进行.近年来,由于群体水平的研究并不能很好地解释一些现象,在单细胞水平探究细菌生长过程所遵循的各种规律成为一种新的趋势.得益于多种单细菌捕获技术的发展,研究者们能够更加方便、合理地在单细胞水平对细菌开展相关研究.对细菌的尺寸调控研究,单细胞数据所呈现的结果与群体研究所得到的信息存在出入,前者能更精准、全面地反映被群体所覆盖的信息,使我们从群体培养所得到的“筛选器(sizer)”与“计时器(timer)”模型转向“加法器(adder)”与“噪声线性谱(noisy linear map)”模型.本文将结合单细菌捕获技术的介绍,简述细菌的各种尺寸调控机制理论与模型,希望有助于研究者快速了解本领域目前的研究进展与相关的基础理论体系.

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.