Spatial partitioning improves the reliability of biochemical signaling

TL;DR

This paper demonstrates that spatial partitioning in cellular membranes enhances biochemical signaling reliability by reducing noise and non-linearity, with an optimal partition size balancing signal fidelity and protein availability.

Contribution

The study provides an exact stochastic model showing how membrane partitioning improves signaling reliability and identifies an optimal partition size consistent with experimental data.

Findings

Partitioning reduces response noise and non-linearity.

An optimal partition size balances reliability and protein presence.

Results are validated with spatial simulations.

Abstract

Spatial heterogeneity is a hallmark of living systems, even at the molecular scale in individual cells. A key example is the partitioning of membrane-bound proteins via lipid domain formation or cytoskeleton-induced corralling. Yet the impact of this spatial heterogeneity on biochemical signaling processes is poorly understood. Here we demonstrate that partitioning improves the reliability of biochemical signaling. We exactly solve a stochastic model describing a ubiquitous motif in membrane signaling. The solution reveals that partitioning improves signaling reliability via two effects: it moderates the non-linearity of the switching response, and it reduces noise in the response by suppressing correlations between molecules. An optimal partition size arises from a trade-off between minimizing the number of proteins per partition to improve signaling reliability and ensuring sufficient proteins per partition to maintain signal propagation. The predicted optimal partition size agrees quantitatively with experimentally observed systems. These results persist in spatial simulations with explicit diffusion barriers. Our findings suggest that molecular partitioning is not merely a consequence of the complexity of cellular substructures, but also plays an important functional role in cell signaling.