From the Nuclear Pore Complex to Smart Artificial Nanochannels

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Human cell stores DNA inside the nucleus. Nuclear pore complexes are large protein complexes on the nuclear envelope, acting like checkpoints for the nuclear import and export. Each nuclear pore complex selects only 0.1 percent of all the protein types and transports them through the nuclear envelope at a rate of around 1000 molecules per second. It is still a mystery how the nuclear pore complex controls the transport of so many different biomolecules with such a high efficiency and selectivity. Understanding this most sophisticated biological nanopore built by nature is expected to inspire the design of next-generation man-made nanopores that will help solve many real-world material problems such as water desalination and energy conversion. The gatekeepers inside the nuclear pore complex are biological polymers (noodle-like molecules) whose structures are highly dynamic and hard to be captured by experiments. In this proposed work the PI will use a theoretical approach to unravel the mystery of the nuclear pore structure. The modeling effort will focus on the functional structure of the gating proteins. Based on a better understanding of the nuclear pore complex, the PI will design smart artificial nanopores functionalized by synthetic polymers to achieve efficient molecular filtering and sensitive response to the environment. The designed nanopores will be computationally optimized and tested by the experimental collaborators on the project. Undergraduate and graduate students will be trained by the PI.One primary feature of the F(phenylalanine)-G(glycine)-Nups is the alternating arrangement of hydrophilic (water-like) and hydrophobic (oil-like) amino acids on their sequences, rendering a complex liquid nano-environment that supports multiple pathways for nuclear transport. It has been heatedly debated whether the amphiphilic phenylalanine-glycine-Nups assume a gel-like or brush-like structure. To address this question, the PI has developed a molecular theory that explicitly accounts for the molecular conformations, electrostatics, hydrophobic interactions, excluded volume effects and acid-base equilibrium at a properly coarse-grained level. Previous work by the PI revealed that the electrostatic and hydrophobic interactions are coupled inside the nuclear pore, leading to a non-additive effect on the nuclear transport. In this research project, the PI will further map the spatial distributions of different hydrophobic functional groups, which will allow for the identification of various nuclear transport pathways. By improving the resolution of the PI?s theoretical microscope, different hypotheses of the nuclear structure can be tested. Using the model developed by the PI, the polymer sequence interaction strength and grafting position can be easily changed to study their effects on the gating performance. The insights from such systematic study will elucidate the design principles for polymer-based synthetic nanopores. The PI will explore the combination of synthetic functional motifs with different stimuli-responses to design nanopores with multiple functions. On the other hand, to take advantage of solid-state materials for artificial nanodevices, the PI will investigate the curvature effect of surface on the self-assembly of grafted/adsorbed polymers. By integrating stimuli-response, sequence-design and curvature-control, the potential of next-generation nanopores inspired and beyond biology will be demonstrated.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.