Biohybrid Membrane Formation by Directed Insertion of Aquaporin into a Solid-State Nanopore

[Image: see text] Biohybrid nanopores combine the durability of solid-state nanopores with the precise structure and function of biological nanopores. Particular care must be taken to control how biological nanopores adapt to their surroundings once they come into contact with the solid-state nanopores. Two major challenges are to precisely control this adaptability under dynamic conditions and provide predesigned functionalities that can be manipulated for engineering applications. In this work, we report on the computational design of a distinctive class of biohybrid active membrane layers, built from the directed-insertion of an aquaporin-incorporated lipid nanodisc into a model alkyl-functionalized silica pore. We show that in an aqueous environment when a pressure difference exists between the two sides of the solid-state nanopore, the preferential interactions between the hydrocarbon tail of the lipid molecules that surround the aquaporin protein and the alkyl group functionalizing the interior surface of the silica nanopore enable the insertion of the aquaporin-incorporated lipid shell into the nanopore by forcing out the water molecules. The same preferential interactions are responsible for the structural stability of the inserted aquaporin-incorporated lipid shell as well as the water sealing properties of the lipid–alkyl interface. We further show that the aquaporin protein stabilized in the alkyl-functionalized silica nanopore preserves its biological structure and function in both pure and saline water, and, remarkably, its water permeability is equal to the one measured in the biological environment. The designed biohybrid membrane could pave the way for the development of durable transformative devices for water filtration.