Artificial shuttle-cargo transport of proteins

Research Project, 2022 – 2025

The machinery of life operates through highly sophisticated mechanisms on the molecular level, many of which are not yet understood. This is especially true for processes involving so called intrinsically disordered molecules.

One fascinating example is the nuclear pore complex (NPC), which controls transport of molecules to the nucleus. Using disordered peptides, the NPC forms a highly selective barrier that only allows specific “shuttle” proteins to pass. The shuttles can even carry “cargo” proteins with them. The cargo would not be able to cross the barrier alone.The goal of this project is to create an artificial shuttle-cargo transport system based on solid state nanopores with polymer brushes (end-grafted chains) on the walls. The brushes form a barrier with disordered morphology. It will be systematically investigated how molecules and particles (shuttles) that have an affinity for the polymer brush interact with it and potentially diffuse through the barrier. The well-controlled artificial system allows different interactions (e.g. electrostatic or hydrophobic) to be tested in different environments. Critical parameters such as number of contact points (multivalency) or barrier density can be easily tuned.The project will increase our understanding of supramolecular chemistry, in particular the entropic contributions from multivalent interactions and conformational changes. This, in turn, is important for understanding several biological processes (not only the NPC).