Complex cells take care of their own

Yeasts are equivalent to lab mice when it comes to understanding how cells work and interact. Scientists test yeast in food fermentation, alcohol production, and also modeling complex cells, such as human cells.

Researchers at the University of Cambridge in the United Kingdom tested yeast once more to better comprehend how cells transfer nutrients to one another and discovered “behaviors” never truly observed before.

“Once a cooperating cell community is established, it has the potential to exhibit higher levels of functioning that would not be possible at the single cell level,” said Kate Campbell, a Ph.D. student at Cambridge and lead researcher of the study. “Foreign cells may, therefore, die as they have not established any type of [nutrient exchange] interaction networks important for survival.”

This essentially means a community of yeast cells efficiently share nutrients, or “biomolecules” known as metabolites, among their own kind. If a yeast cell is introduced and did not develop from that culture, it would not get to eat with the rest of the family.

These findings were published October 26 in the open-­access journal, eLife, and offer new insight on complex cell interaction that takes place in animals, plants and single-­cell eukaryotes such as yeast.

“I liked that this work highlights one of the amazing mechanisms that cells develop to survive,” said Maria Olin­-Sandoval, a cellular biologist at the University of Cambridge. She was not a part of Campbell’s research team, but she also specializes in cell nutrient consumption.

One of the fundamental reasons why these findings are so important is because of variation, Campbell said. “Between individual cells, there can be various levels of variation, despite cells having the same genetic content.”

“You can observe in these populations that it does not necessarily mean that all the cells are exactly the same, but that the population is composed of cells that can survive due to metabolic cooperation,” Olin-­Sandoval said.

Going back to introductory biology, one should remember that cells replicate and share DNA, but sometimes the components of the cell changes in the process. The study noted that cells can change and respond in a variety of ways to internal and external changes. Environmental stressors like intense hot or cold temperatures and gene expression can affect a cell’s metabolism.

“It's like having two identical twins, and letting one grow up in Sweden and the other in Texas,” Campbell said. “They would perhaps respond differently being moved to the Arctic – an environmental stressor – as a result of their different previous environments and life histories.”

This research shows that after different variables affect a single cell’s metabolism, changes begin to occur in the community.

“My research proposes that metabolism may be a cause for cell­-to-­cell variation,” she said. “We suggest that the export activities of one cell may affect the metabolism of another neighboring cell. As cells export an essential nutrient, this can cause other cells to switch from self­-synthesis to uptake.”

Uptake is the process in which one cell shares its nutrients and other cells use them. In colonies, this can be far more efficient. “Which makes sense. Why would you use expensive multistep molecular components in the cell to make your nutrient when you can import the end product already available?” Campbell asked.

The research team had to account for these variables and more, especially because there is a lot going on in a natural environment as opposed to the lab environment.

“The cells were genetically modified to enable cells to export higher amounts of nutrients,” Campbell said. “In the wild, however, cells respond dynamically to changes in nutrient abundance, which seems logical considering that nutrient availability would also fluctuate.”

Genetic modification was used in order to keep the cells at a “growing phase,” which is a time in a cell’s life where it can create and spew out metabolites for others in the family to use.

We observed that the extracellular content between wild yeast cells in a community was highly similar between [the experimental, genetically modified group],” Campbell said.

These confirmations in self-­establishing communities and sharing nutrients are also beginning to be considered for other areas of research, she said. If cells can isolate foreign bodies that may harm the other healthy cells, this may be a good way to think in terms of medicine.

Some applications, she explained, could be in destroying cancer cells, finding brain cells with misfolded proteins that cause neurological disorders like Alzheimer’s disease, or destroying harmful gut bacteria that cause food poisoning and ulcers.

“The metabolic cooperation is a very interesting topic that has been studied in different types of cell communities including tumor cells,” Olin­-Sandoval said. “Many fundamental cellular processes are highly conserved between yeasts and human cells.”

Yeast cells are an essential model for cellular and microbiology, and these findings can represent a lot of the diseases and cancers that humans suffer from. Olin­-Sandoval said this study’s results “can contribute much more than we realize to the knowledge of what could be happening in human cells and disease.”

“Our results certainly provide a previously unconsidered and important insight into potential microbial interactions that can occur,” Campbell said. “We can now explore the possible interaction networks that cells may establish which may also be significant in number. We also confirmed that cells prefer uptake over self ­synthesis for our tested essential nutrients which has enormous implications for microbial research.”