The spatial structure of cell signaling systems

TL;DR

This paper proposes a new multiscale view of cell signaling, emphasizing dynamic, spatially organized clusters and allosteric interactions over traditional diffusion-based models, linking structure to cellular function.

Contribution

It introduces a novel perspective on cell signaling, highlighting the role of transient clusters and multiscale spatial organization in cellular behavior.

Findings

Cell signaling involves dynamic clusters from nanometers to micrometers.

Membrane domains and actin cytoskeleton are key in spatial organization.

Signaling is driven by allosteric interactions rather than just molecular collisions.

Abstract

The spatial structure of the cell is highly organized at all levels: from small complexes and assemblies, to local nano- and micro-clusters, to global, micrometer scales across and between cells. We suggest that this multiscale spatial cell organization also organizes signaling and coordinates cellular behavior. We propose a new view of the spatial structure of cell signaling systems. This new view describes cell signaling in terms of dynamic allosteric interactions within and among distinct, spatially organized transient clusters. The clusters vary over time and space and are on length scales from nanometers to micrometers. When considered across these length-scales, primary factors in the spatial organization are cell membrane domains and the actin cytoskeleton, both also highly dynamic. A key challenge is to understand the interplay across these multiple scales, link it to the physicochemical basis of the conformational behavior of single molecules, and ultimately relate it to cellular function. Overall, our premise is that at these scales, cell signaling should be thought of not primarily as a sequence of diffusion-controlled molecular collisions, but instead transient, allostery-driven cluster re-forming interactions.