  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.
