How fast does a stressed cell react?

This has now been done by CNRS researcher Pascal Hersen (1) and the team led by Sharad Ramanathan at the Center for Systems Biology (Harvard University). Using a simple and innovative measuring device that they developed, the researchers have confirmed the hypothesis that above a certain stimulation frequency, the yeast cell no longer responds to osmotic stress (2).

They are now able to measure the rate of reaction to such stress, and above all, modify the reaction rate by eliminating certain genes. This work opens up new prospects for biological engineering. The idea is to construct cells with novel biological functions and whose dynamics can be controlled. These findings have been published on line on the web site of the journal /PNAS/.

Place a little salt on a cell and it immediately shrinks. This phenomenon is caused by the difference in salinity inside and outside the cell. To restore equilibrium between the concentrations, the cell releases some water, which reduces its size. In order to return to normal size, the cell undergoes a series of reactions that are essential for the efficient working of its regulation and adaptation processes. In the yeast Saccharomyces cerevisiae, a model eukaryotic (3) system, such a cascade has been well described. However, its dynamics remain poorly understood. A cell needs to react at the right rate in order to ensure its survival. It is therefore essential to understand the dynamics of cell response to environmental stress.

To this end, Pascal Hersen, CNRS researcher at the Complex Systems and Matter Laboratory (CNRS / Université Paris 7), and his US colleagues decided to study how and at what rate yeast responds and adapts to environmental stress. Using a simple device that makes it possible to follow the behavior of individual cells, they created an environment which periodically brings about disequilibrium. In this way they were able to determine the dynamic properties of cell response.

Their first observation was that when the frequency is too high, the size of the cells doesn't change. There simply isn't enough time for the transfer of water through the cell membrane to take place. On the other hand, for lower frequencies (input of disequilibrium every 10 seconds), the cells shrink and swell periodically, faithfully following the fluctuations of the disequilibrium. However, in this range of frequencies, there isn't enough time for the cascade of reactions to be activated between two cycles. There is thus a decoupling between the mechanical response and the biological response. It is only when the period is more than around ten minutes that the biological reactions are activated and follow one another 'naturally', while at the same time being coupled to the mechanical response of the cell. This frequency is therefore characteristic of the response dynamics in yeast, which is unable to faithfully follow changes in its environment that are too rapid, i.e. a period of less than ten minutes.

Finally, by eliminating certain genes from the yeast, the researchers showed that this cascade can be significantly slowed down. They now hope to understand how the quantity and nature of the proteins affects the dynamics of these reactions, and how they might eventually be able to speed them up or slow them down. Being able to manipulate them in this way opens up new prospects in synthetic biology (4) for the design of cells with novel functions, whose dynamics of response to stress can be controlled.

(1) Unité Matière et systèmes complexes (MSC, CNRS / Université Paris 7).

(2) Osmotic stress is caused by a difference in concentration of solute (such as salt) on either side of the cell membrane. Osmosis is the name given to the phenomenon of a return to equilibrium by diffusion of water through the membrane.

(3) A living organism which has a nucleus separated from the cytoplasm by a membrane and containing DNA.

(4) Synthetic biology is the engineering of living organisms. It consists in synthesizing complex systems based on biology which carry out functions that don't exist in nature.