Discovery of viscoadaptation, a homeostatic stress response
Cells must precisely orchestrate thousands of reactions in time and space. Yet reaction kinetics are highly dependent on environmental conditions that can be highly variable, such as temperature and energy availability. “Warm-blooded” organisms address ambient temperature variations by controlling their internal temperature, but most organisms remain at the whim of ambient temperature. How a complex, diffusion-based system such as a cell can function across large temperature ranges has been a thermodynamic mystery.
When measuring the rate at which RQC components and the ribosome interact, we noticed that certain environmental conditions drastically reduced the rate of physical interactions between proteins. This observation led to our discovery that budding yeast counteract the effects of environmental fluctuations in temperature and nutrient availability by modulating their viscosity, thereby influencing the rate of cellular processes. We propose that this new mechanism of cellular adaptation, which we termed “viscoadaptation”, occurs via the production of two carbohydrates, trehalose and glycogen, whose levels in the cell we showed adjust the viscosity of the intracellular environment (Persson et al., 2019). We demonstrated that viscoadaptation slows the motion of individual proteins at high temperatures or in nutrient-poor conditions while keeping cytosolic proteins soluble. Viscoadaptation functions as both an acute stress response and a homeostatic mechanism, allowing cells growing at 22℃ to 40℃ to maintain constant rates of intracellular diffusion and diffusion-controlled chemical reactions. Multiple conditions that lower ATP levels trigger viscoadaptation, suggesting that viscoadaptation may link the availability of energy to the control of reaction rates in cells. Based on the ubiquity of trehalose and glycogen in diverse lifeforms, viscoadaptation may be an ancient and widespread adaptation mechanism that affects myriad cellular phenomena through the regulation of a fundamental biophysical property, viscosity.
Back to Research