Thermodynamic Uncertainty Relation in the interlinked cascade of RabGTPases

TL;DR

This paper investigates the Thermodynamic Uncertainty Relation in the interlinked Rab GTPase cascade, demonstrating that interlinking enhances precision and robustness at far from equilibrium, with implications for disease dynamics.

Contribution

It provides the first numerical proof of TUR in interlinked Rab GTPase models and reveals how interlinking improves thermodynamic efficiency and system robustness.

Findings

Interlinked Rab GTPases increase thermodynamic cost and precision.

Far from equilibrium, interlinked systems outperform single species.

Interlinked cascades exhibit tunable rate constants and robustness.

Abstract

We model the well-known interlinked cascade of Rab GTPases found in eukaryotic cells by using a network of Markov states to investigate the universal Thermodynamic Uncertainty Relation for the non-equilibrium system. First, we prove numerically the TUR in both single Rab species model and the interlinked two Rab species model. Our results show that when two Rab GTPase proteins are interlinked at far from equilibrium, the thermodynamic cost and hence precision is greatly enhanced as compared to single species switching. This implies that at far from equilibrium, the proteins tries to optimise the precision of the performance of their biomolecular processes by forming interlinks in the cascade. Again,our results imply that the interlinked cascade (or oscillator) can achieve a range of tunable rate constants (or frequencies) which suggests a means of maintaining its robustness. Lastly, we highlight a close relation between thermodynamic cost-precision, triangular motifs and disease dynamics.