Living Systems Might Require a Fourth Law of Thermodynamics

The principles of thermodynamics, particularly aspects like heat and entropy, provide valuable methods for assessing how far a system of ideal particles is from achieving equilibrium. Nevertheless, it’s uncertain if the existing thermodynamic laws adequately apply to living organisms, whose cells are complexly intertwined. Recent experiments involving human cells might pave the way for the formulation of new principles.

Thermodynamics plays a crucial role in living beings, as their deviations from equilibrium are critical characteristics. Cells, filled with energetic molecules, behave differently than simple structures like beads in a liquid. For instance, living cells maintain a “set point,” operating like an internal thermostat with feedback mechanisms that adjust to keep functions within optimal ranges. Such behaviors may not be effectively described by classical thermodynamics.

N. Narinder and Elisabeth Fischer-Friedrich from the Technical University of Dresden aimed to comprehend how the disequilibrium in living systems diverges from that in non-living ones. They carried out their research using HeLa cells, a line of cancer cells derived from Henrietta Lacks in the 1950s without her consent.

Initially, the scientists employed chemicals to halt cell division, then analyzed the outer membranes of the cells using an atomic force microscope. This highly precise instrument can engage with structures just nanometers in size, enabling researchers to measure how much the membranes fluctuated and how these variations were affected by interference with cell processes, such as hindering the development of certain molecules or the movement of proteins.

The findings showed that conventional thermodynamic models used for non-living systems did not fully apply to living cells. Notably, the concept of “effective temperature” was found to be misleading, as it fails to account for the unique behaviors of living systems.

Instead, the researchers emphasized the significance of “time reversal asymmetry.” This concept examines how the distinctions in biological events (like molecules repeatedly joining to form larger structures only to break apart again) differ when observed forwards versus backwards in time. These asymmetries are directly linked to the functional purposes of biological processes, such as survival and reproduction, according to Fischer-Friedrich.

“In biology, numerous processes are reliant on a system being out of equilibrium. Understanding how far the system deviates is crucial,” states Chase Brodersz from Vrije Universiteit Amsterdam. Recent findings have unveiled a promising new metric for assessing this deviation.

This development marks a significant stride toward enhancing our knowledge of active biological systems, as observed by Yair Shokev at Tel Aviv University. He notes the novelty and utility of the team successfully measuring time-reversal asymmetry alongside other indicators of non-equilibrium simultaneously.

However, to understand life through the lens of thermodynamic principles, further advancements are necessary. Fischer-Friedrich and her team aspire to formulate a concept akin to the fourth law of thermodynamics, specifically applicable to organisms with defined processes. They are actively investigating physiological observables—key parameters measurable within cells—from which such laws could potentially be derived.