Active transport improves the precision of linear long distance molecular signalling

TL;DR

This paper demonstrates that intermittent active transport enhances molecular signalling precision in cells by reducing noise and improving equilibration, especially over large distances, through a theoretical analysis of molecular motion.

Contribution

It introduces a linear response theory to quantify how active transport improves signalling accuracy by disrupting recurrence in molecular motion.

Findings

Active transport speeds up concentration equilibration.

Intermittent active excursions reduce noise in one-dimensional systems.

Theoretical limits of signalling precision are derived.

Abstract

Molecular signalling in living cells occurs at low copy numbers and is thereby inherently limited by the noise imposed by thermal diffusion. The precision at which biochemical receptors can count signalling molecules is intimately related to the noise correlation time. In addition to passive thermal diffusion, messenger RNA and vesicle-engulfed signalling molecules can transiently bind to molecular motors and are actively transported across biological cells. Active transport is most beneficial when trafficking occurs over large distances, for instance up to the order of 1 metre in neurons. Here we explain how intermittent active transport allows for faster equilibration upon a change in concentration triggered by biochemical stimuli. Moreover, we show how intermittent active excursions induce qualitative changes in the noise in effectively one-dimensional systems such as dendrites. Thereby they allow for significantly improved signalling precision in the sense of a smaller relative deviation in the concentration read-out by the receptor. On the basis of linear response theory we derive the exact mean field precision limit for counting actively transported molecules. We explain how intermittent active excursions disrupt the recurrence in the molecular motion, thereby facilitating improved signalling accuracy. Our results provide a deeper understanding of how recurrence affects molecular signalling precision in biological cells and novel diagnostic devices.