We may need a fourth law of thermodynamics for living systems

The physics of thermodynamics, which includes quantities such as heat and entropyoffers well-established tools for determining how far from equilibrium an idealized particle system is. But when it comes to life, with its complex, interconnected cells, it's unclear whether our current set of thermodynamic laws are sufficient—and a series of experiments involving human cells could be the first step toward creating new ones.

Thermodynamics is important to life because getting out of equilibrium one of its key properties. But because cells are filled with molecules that actively consume energy, the cell's state is different from, say, a bunch of balls floating in a liquid. For example, biological cells have what is called a set point, which means they behave as if they were following an internal thermostat. There is a feedback mechanism that returns them to the set value, which allows them to continue to function. It is precisely this behavior that is not easily captured by classical thermodynamics.

N Narinder And Elisabeth Fischer-Friedrich at the Dresden University of Technology in Germany wanted to gain a detailed understanding of how disequilibrium in living systems differs from disequilibrium in a non-living system. They did this with human HeLa cells, a line of cancer cells commonly used in scientific research, that were taken without consent from an African American woman named Henrietta Lacks in the 1950s.

The researchers first used chemicals to stop the cells dividing midway and then probed their outer membranes with the tip of a needle. atomic force microscopewhich can precisely interact with objects just a fraction of a nanometer wide. This made it easier to assess how each cell's membrane vibrated (how much the microscope tip wiggled) and how these vibrations changed when the researchers interfered with certain cellular processes, for example by interrupting the morphing of certain molecules or the movement of certain proteins.

They found that for these oscillations, one standard thermodynamic “recipe” for explaining the behavior of a nonliving system is no longer completely accurate. In particular, the idea of ​​”effective temperature” turned out to be inaccurate. This idea is intended to capture something similar to our understanding of how temperature increases when we throw a system like a pot of water out of balance by heating it.

But researchers have concluded that a more useful quantity for determining the degree of disequilibrium in life is a property called “time reversal asymmetry.” This examines the extent to which a given biological process (for example, molecules combining repeatedly into larger molecules before breaking apart again) will be different. if he ran backwards instead of forwards during. The presence of time reversal asymmetries may be directly related to the fact that biological processes serve purposes such as survival and propagation, Fischer-Friedrich says.

“We know in biology that there are a lot of processes that do depend on the system being in equilibrium, but what's really important is knowing how far out of equilibrium the system is,” says Chase Broders at Vrije Universiteit Amsterdam in the Netherlands. The new study identifies valuable new tools to establish this fact, he said.

This is an important step towards improving our understanding of active biological systems, says Yair Shokef at Tel Aviv University in Israel. He says the fact that the team was able to experimentally measure not only time-reversal asymmetry, but several other measures of disequilibrium simultaneously, is both novel and useful.

However, we may have to take many more steps if we want to understand life using thermodynamic principles. Fischer-Friedrich says the team ultimately wants to derive something like the fourth law of thermodynamics, which applies only to living matter where processes have a given point. They are already working to identify physiological observables—specific things that can be measured in cells—where they could begin to derive such a law.