Adaptive flexibility of cells through nonequilibrium entropy production

TL;DR

This paper introduces a nonequilibrium physics framework to understand how structural variability in sarcomeres facilitates cellular adaptation by modulating energy barriers for remodeling, highlighting the functional role of disorder.

Contribution

It presents a novel theoretical approach linking entropy and structural randomness to cellular adaptability, emphasizing the functional significance of sarcomere variability.

Findings

Higher entropy in nonmuscle cells lowers remodeling energy barriers.

Ordered sarcomeres in muscle cells correspond to higher stability.

Disorder in sarcomeres enables flexible adaptation.

Abstract

Cellular adaptation to environmental changes relies on the dynamic remodeling of subcellular structures. Among these, sarcomere structures are fundamental to the organization and function of the cytoskeletal architecture. In muscle-type cells, sarcomeres exhibit ordered structures of consistent lengths, optimized for stable force generation. By contrast, nonmuscle-type cells display a higher degree of structural variability, with sarcomeres of varying lengths that contribute not only to force generation but also to adaptive remodeling upon environmental cues. While these differences in sarcomere structures have traditionally been attributed to the unique properties of specific proteins expressed in each cell type, the functional implications of such structural variability remain unclear. Here, we present a nonequilibrium physics framework to elucidate the role of sarcomere variability in cytoskeletal adaptation. Specifically, we demonstrate that the effective binding strength of sarcomere components can be evaluated by analyzing structural randomness using Shannon entropy. The increased entropy associated with the inherent randomness of sarcomere structures in nonmuscle-type cells lowers the energy barrier for cytoskeletal remodeling, enabling flexible adaptation to environmental demands. Meanwhile, the ordered sarcomere arrangements in muscle-type cells correspond to higher binding energies and more stable cytoskeletal configurations. Although structural disorder is often regarded as unfavorable in terms of stability, our study suggests that it plays a key role in enabling adaptive responses in cellular systems.