Discrete 3D Model of Molecular Diffusion Through the Nuclear Pore Complex

Abstract

Nuclear pore complexes (NPCs) are passageways that exist within the nuclear envelope (NE) of a eukaryotic cell. Molecular cargo travel through the passageways to either import to the nucleus or export to the cytoplasm of the cell. Efficient export of certain cargo is necessary for maintained health of a cell, and hence, the organism. Traditional methods of observing NPCs lack resolution great enough for scientists to study the many interactions that take place inside of the complex. A discrete 3D model of the molecular diffusion was built to understand how cargo moves through the NPCs and how to improve import and export efficiency of particular molecules. The basis of the model is a Langevin equation that was customized to the environment of the central channel of a NPC. The model incorporated not only the Brownian motion of the molecules, but also the geometry of the channel, the diffusion coefficient for molecules in the fluid of the central channel, and a potential energy (PE) function to describe drifting affects by the dense layers of phenylalanine-glycine (FG) repeats located in the channel and a concentration of transport receptors located on either ends of the NPC. The model simulated the movement of spherical molecules through the NPC and kept track of their location during their transport. The model showed that the cargo’s movement has a distinct dependence on the PE function. The model can be further, and easily, manipulated and used for more comparisons to experimentally determined export efficiency for different cargo.