Using Single-Cell Microfluidics to Measure Cellular Memory*

Microbial populations of genetically identical cells can contain different phenotypes, with each cell's phenotype changing over time. Tolerant phenotypes confer protection from environmental stresses. By restoring the original population, a few tolerant cells can save the entire population from extinction. Their main downside is slower growth, implying a trade-off between maximizing growth and ensuring survival during stress.

Well-adapted populations should contain a few, but minimal, tolerant cells to survive periods of stress, so their proportions vary in different environments (frequent/rare stress). Since they are partly given by how much time each cell spends in each phenotype ("cellular memory") we expect cellular memory to vary with environment.

We examine this in yeast containing a synthetic gene circuit, which enables separate control of growth and survival. This allows us to easily measure phenotype by tracking the fluorescence of a single tagged protein. We trap single cells from mutant strains, evolved in different environments, in a microfluidic chip. By reading off their fluorescence time courses, we measure the cellular memory of each to find out how they have adapted to their environment.