The macroscopic effects of microscopic heterogeneity

TL;DR

This paper reviews how microscopic heterogeneity in cellular environments, driven by molecular structures and intrinsic factors, can lead to significant macroscopic effects on cell signaling behavior.

Contribution

It provides a comprehensive overview of mechanisms by which microscopic heterogeneity influences large-scale cellular functions, integrating recent microscopy and modeling advances.

Findings

Correlations between molecules significantly affect cell signaling.

Both imposed and intrinsic heterogeneities contribute to cellular behavior.

Microscopic effects can be amplified to macroscopic outcomes.

Abstract

Over the past decade, advances in super-resolution microscopy and particle-based modeling have driven an intense interest in investigating spatial heterogeneity at the level of single molecules in cells. Remarkably, it is becoming clear that spatiotemporal correlations between just a few molecules can have profound effects on the signaling behavior of the entire cell. While such correlations are often explicitly imposed by molecular structures such as rafts, clusters, or scaffolds, they also arise intrinsically, due strictly to the small numbers of molecules involved, the finite speed of diffusion, and the effects of macromolecular crowding. In this chapter we review examples of both explicitly imposed and intrinsic correlations, focusing on the mechanisms by which microscopic heterogeneity is amplified to macroscopic effect.