Physical principles of selective transport into and out of the cell nucleus

Nuclear pore complexes (NPCs) regulate macromolecular transport into and out of the cell nucleus. NPCs have remarkable transport properties: They show size selectivity, impeding unspecific transport of cargos 6 nm diameter yet facilitating translocation of much larger cargos (up to ~40 nm diameter) that meet certain biophysical criteria, such as ribosome subunits and intact or only partially disassembled viruses.

The NPC is therefore an exceptionally efficient biological filter. Its selectivity relies on natively unfolded nuclear pore proteins that pack in a disordered way in the NPC channel. Because of this unfolded and disordered nature and the location of these proteins deep inside the NPC channel, the mechanism of NPC selectivity remains a difficult problem to address via structural and biochemical methods alone.

With this project, we build on recent successes (by ourselves and others) in using polymer physics to understand the collective behaviour of the nuclear pore proteins in the transport barrier. We will develop different theoretical and computational approaches, including classical density functional theory, Monte Carlo, and coarse-grain molecular dynamics for quantitative comparisons with experimental data on nanoscale model systems for the NPC transport barrier and on the NPC itself. Ultimately, we aim to develop a full working and quantitatively accurate model for NPC selectivity.