New review illuminates how thermodynamics sets boundaries for life's functions

A comprehensive new review published in Quantitative Biology synthesizes decades of research showing how thermodynamic principles impose fundamental constraints on biological systems. The review bridges physics and biology by analyzing how stochastic thermodynamics—a framework describing energy exchanges in microscopic systems—helps explain limitations across diverse biological functions.

Scientists from Tsinghua University in China and École Polytechnique Fédérale de Lausanne (EPFL) in Switzerland have compiled and analyzed research demonstrating how living systems operate within physical boundaries set by nonequilibrium thermodynamics, from molecular machines to collective cellular behaviors.

"Physics and biology, while sharing a common goal of understanding the natural world, employ distinct paradigms and terminologies," explains Yuansheng Cao from Tsinghua University. "Our review bridges this disciplinary gap by applying the principles and methodologies of physics to elucidate biological phenomena."

The authors explore how recent advances in stochastic thermodynamics provide a powerful framework for understanding constraints on mesoscopic biological systems—those operating at scales between molecular and cellular levels. The review traces the development of key concepts like the fluctuation theorem, thermodynamic uncertainty relation, and nonequilibrium response bounds.

"Among the relevant subfields of physics, thermodynamics provides some of the most universal constraints on biological systems," notes Shiling Liang from EPFL. "We emphasize the interconnectedness of kinetics and energetics within this framework, focusing on how network topology, kinetics, and energetics influence functions in thermodynamically consistent models."

The review systematically analyzes research across multiple biological domains. For molecular machines like motor proteins, it describes how thermodynamic uncertainty relations establish fundamental trade-offs between precision and energy consumption. In error correction mechanisms such as DNA replication, the authors synthesize research showing how kinetic proofreading consumes energy to achieve accuracy levels impossible under equilibrium conditions.

The scientists also examine research on biological sensing systems, where cells demonstrate remarkable sensitivity to environmental changes while operating within thermodynamic constraints. The review highlights how studies of collective behaviors reveal additional energy requirements for coordinating components into functional systems.

"This review aims to bridge physics and biology by fostering a quantitative understanding of biological functions," the authors write. "While stochastic thermodynamics offers valuable insights, structure and topology also play critical roles in determining biological function. Integrating diverse biological data and constraints into thermodynamic frameworks remains a key challenge."

By bringing together research across disciplines, the review provides a comprehensive perspective on how living systems navigate physical constraints while performing their remarkable functions.

DOI: 10.1002/qub2.75