Too Much of a Good Thing? Why Cells Throw Away Essential Chemicals

The human body can be a little pessimistic, constantly hoarding any excess nutrients just in case things go south. From an evolutionary perspective, this makes sense—when you don’t know where your next meal is coming from, being able to hang onto your resources can make the difference between life and death. Cells on the other hand, have long puzzled researchers with their tendency to throw away essential chemicals without any apparent regard for the future.

“The chemicals in a cell can basically be classified into two groups: metabolites and proteins,” explains Jumpei Yamagishi, a first-year graduate student at the University of Tokyo. As cells take in nutrients, such as sugars, fats, and proteins, they use the comparatively small metabolites, like amino acids, as intermediaries to break down the nutrients and release the energy stored in their chemical bonds. Without metabolites, the cells can quite literally starve to death in a sea of abundance—yet they persist in releasing the essential molecules to their surroundings.

As part of his research in Dr. Kunihiko Kaneko’s lab, Yamagishi wanted to apply a new physics perspective to this biological puzzle. The team quickly realized that the chain of chemical reactions involved in the breakdown of nutrients could be approached as a problem in nonlinear dynamics, since the concentration of each molecular component constantly changes as it reacts. This creates a feedback loop, since statistical physics says that the probability of each chemical reaction relies on the relative molecular concentrations. At the same time, the successful degradation of nutrients enables the cell’s growth, which dilutes the concentration of all chemicals contained within the cell.

Using the tenets of nonlinear dynamics and statistical physics, the research group developed a mathematical model encompassing each reaction within a typical cell’s metabolism. By focusing on the steady-state—the stable solutions that allow the cell to continue metabolizing—they found that in some cases it is advantageous to leak metabolites, mathematically speaking. “By secreting out some chemicals, the internal balance between complicated nonlinear reactions is altered,” says Yamagishi. Rather than holding onto metabolites that might be useful in the future, cells selectively release the chemicals to create the ideal environment for the quick decomposition of nutrients.

As an interesting addendum to the project, Kaneko says that this trait points to a possible evolutionary step towards symbiosis, which is a partnership between two or more types of organisms. “Secretion is good for these cells,” he says, “but then the environment is ‘polluted’ by these chemicals.” This phenomenon can create a special niche for another type of cell that needs the leaked chemicals, leading to a rudimentary symbiotic relationship between cell types.

Figure 1. Astrangia poculata coral off Rhode Island have a symbiotic relationship with photosynthesizing protists. This research shows a mathematical model for the development of symbiosis. Image credit: Rotjen Lab via Wikimedia Commons

In fact, a longstanding principle called Gause’s limit states that the number of coexisting species is limited by the number of nutrient niches in the environment; constant competition for the same nutrients kills off all but the strongest of cells. “But we found that each cell’s selfish secretion of metabolites can increase this limit by creating new niches,” Yamagishi says. The leakage of each metabolite is entirely connected to the cell’s desire for rapid growth, but it can also allow other cells to flourish and potentially release other types of metabolites for uptake. Hey—maybe sometimes it pays to live in the moment?

—Eleanor Hook

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