Yeast cell responses and survival during periodic osmotic stress are controlled by glucose availability.

Natural environments of living organisms are often dynamic and multifactorial, with multiple parameters fluctuating over time. To better understand how cells respond to dynamically interacting factors, we quantified the effects of dual fluctuations of osmotic stress and glucose deprivation on yeast cells using microfluidics and time-lapse microscopy. Strikingly, we observed that cell proliferation, survival, and signaling depend on the phasing of the two periodic stresses. Cells divided faster, survived longer, and showed decreased transcriptional response when fluctuations of hyperosmotic stress and glucose deprivation occurred in phase than when the two stresses occurred alternatively. Therefore, glucose availability regulates yeast responses to dynamic osmotic stress, showcasing the key role of metabolic fluctuations in cellular responses to dynamic stress. We also found that mutants with impaired osmotic stress response were better adapted to alternating stresses than wild-type cells, showing that genetic mechanisms of adaptation to a persistent stress factor can be detrimental under dynamically interacting conditions.

Optogenetic spatial patterning of cooperation in yeast populations.

Microbial communities are shaped by complex metabolic interactions such as cooperation and competition for resources. Methods to control such interactions could lead to major advances in our ability to better engineer microbial consortia for synthetic biology applications. Here, we use optogenetics to control SUC2 invertase production in yeast, thereby shaping spatial assortment of cooperator and cheater cells. Yeast cells behave as cooperators (i.e., transform sucrose into hexose, a public good) upon blue light illumination or cheaters (i.e., consume hexose produced by cooperators to grow) in the dark. We show that cooperators benefit best from the hexoses they produce when their domain size is constrained between two cut-off length-scales. From an engineering point of view, the system behaves as a bandpass filter. The lower limit is the trace of cheaters' competition for hexoses, while the upper limit is defined by cooperators' competition for sucrose. Cooperation mostly occurs at the frontiers with cheater cells, which not only compete for hexoses but also cooperate passively by letting sucrose reach cooperators. We anticipate that this optogenetic method could be applied to shape metabolic interactions in a variety of microbial ecosystems.