Artificial Nuclear Pore Complexes with Exceptionally Selective Shuttle-Cargo Transport

Journal article, 2026

The nuclear pore complex (NPC) is a large protein assembly that controls transport of macromolecules to or from the nucleus in eukaryotic cells. It is capable of facilitated transport in which "cargo" species can bind to "shuttles", which specifically translocate the NPC, while the cargo alone cannot pass. In order to better understand the transport mechanism, attempts have been made to reconstruct the NPC transport using synthetic systems (bottom-up). However, it has proven difficult to achieve a functioning shuttle-cargo transport mechanism, in particular with high selectivity. Here, we present fully artificial NPCs based on heteromolecular polymer complexation. Polymer brushes consisting of poly(hydroxyethyl acrylamide) are prepared on solid-state nanopores to form a barrier that generally only allows small molecules (a few kg/mol) to pass. Still, at lowered pH, multivalent interactions with poly(methacrylic acid) enable efficient transport of this polymer through the brush barrier (predicted max rate >1000 molecules per pore per second). By fine-tuning the affinity, which is strongly dependent on factors such as pH and molecular weight, we show that the polymer shuttles can diffuse through the brush barrier without strongly altering its morphology. As a mimic of nucleic acid export through the NPC, we show that DNA cargo strands conjugated to the polymer shuttles translocate the pores, even though they are too large to pass in their free form. We consider the selectivity of our system to be exceptional, since there is no detectable leakage of unconjugated macromolecules, not even in the presence of free transport shuttles. Besides being of fundamental interest to understand soft matter in general and the NPC in particular, the possibility to switch transport on/off with pH enables unique applications of nanopore-based structures. As an example, we show secure, tether-free, and noninvasive trapping of molecules inside nanoscale chambers a few attoliters in volume under physiological conditions.