Percolation transition prescribes protein size-specific barrier to passive transport through the nuclear pore complex

Nuclear pore complexes (NPCs) control biomolecular transport in and out of the nucleus. Disordered nucleoporins in the complex's pore form a permeation barrier, preventing unassisted transport of large biomolecules. Here, we combine coarse-grained simulations of experimentally derived NPC structures with a theoretical model to determine the microscopic mechanism of passive transport. Brute-force simulations of protein transport reveal telegraph-like behavior, where prolonged diffusion on one side of the NPC is interrupted by rapid crossings to the other. We rationalize this behavior using a theoretical model that reproduces the energetics and kinetics of permeation solely from statistics of transient voids within the disordered mesh. As the protein size increases, the mesh transforms from a soft to a hard barrier, enabling orders-of-magnitude reduction in permeation rate for proteins beyond the percolation size threshold. Our model enables exploration of alternative NPC architectures and sets the stage for uncovering molecular mechanisms of facilitated nuclear transport. Combining realistic coarse-grained simulations with a percolation transition theory, this study elucidates the microscopic mechanism that governs the selectivity of passive, unassisted transport through the nuclear pore complex.

Automated summary

This study combines coarse-grained simulations and a theoretical model to elucidate the microscopic mechanism governing the selectivity of passive, unassisted transport through the nuclear pore complex. The model reproduces the energetics and kinetics of permeation solely from statistics of transient voids within the disordered mesh, enabling exploration of alternative NPC architectures.