Connectivity, clusters, and transport: use of percolation concepts and atomistic simulation to track intracellular ion migration

The cytoskeleton is an intracellular highway system, teaming with signalling ions that zip from site to site along filaments. These tiny particles alternately embrace and slip free of protein receptors with wide-ranging affinities, as they propagate in a blur of motion along cytoskeletal corridors at transport rates far exceeding ordinary diffusive motion. Recent experimental breakthroughs have enabled optical tracking of these single ion-binding events in the physiological and diseased states. However, traditional continuum modelling methods have proven ineffective for modelling migration of biometals such as copper and zinc, whose cytosolic concentrations are putatively vanishingly small, or very tightly controlled. Rather, the key modelling problem that must be solved for biometals is determination of the optimal placement of biosensors that bind and detect the metal ions within the heterogeneous environment of the cell. We discuss herein how percolation concepts, in combination with atomistic simulation and sensor delivery models, have been used to gain insights on this problem, and a roadmap for future breakthroughs.