Bioinspired artificial water channels aim to combine the high permeability and selectivity of biological aquaporin (AQP) water channels with chemical stability. Here, we carefully characterized a class of artificial water channels, peptide-appended pillar [5]arenes (PAPs). The average single-channel osmotic water permeability for PAPs is 1.0(±0.3) × 10 −14 cm 3 /s or 3.5(±1.0) × 10 8 water molecules per s, which is in the range of AQPs (3.4∼40.3 × 10 8 water molecules per s) and their current synthetic analogs, carbon nanotubes (CNTs, 9.0 × 10 8 water molecules per s). This permeability is an order of magnitude higher than first-generation artificial water channels (20 to ∼10 7 water molecules per s). Furthermore, within lipid bilayers, PAP channels can self-assemble into 2D arrays. Relevant to permeable membrane design, the pore density of PAP channel arrays (∼2.6 × 10 5 pores per μm 2 ) is two orders of magnitude higher than that of CNT membranes (0.1∼2.5 × 10 3 pores per μm 2 ). PAP channels thus combine the advantages of biological channels and CNTs and improve upon them through their relatively simple synthesis, chemical stability, and propensity to form arrays.artificial aquaporins | artificial water channels | peptide-appended pillar [5]arene | single-channel water permeability | two-dimensional arrays T he discovery of the high water and gas permeability of aquaporins (AQPs) and the development of artificial analogs, carbon nanotubes (CNTs), have led to an explosion in studies aimed at incorporating such channels into materials and devices for applications that use their unique transport properties (1-9). Areas of application include liquid and gas separations (10-13), drug delivery and screening (14), DNA recognition (15), and sensors (16). CNTs are promising channels because they conduct water and gas three to four orders of magnitude faster than predicted by conventional Hagen-Poiseuille flow theory (11). However, their use in large-scale applications has been hampered by difficulties in producing CNTs with subnanometer pore diameters and fabricating membranes in which the CNTs are vertically aligned (4). AQPs also efficiently conduct water across membranes (∼3 billion molecules per second) (17) and are therefore being studied intensively for their use in biomimetic membranes for water purification and other applications (1, 2, 18). The largescale applications of AQPs is complicated by the high cost of membrane protein production, their low stability, and challenges in membrane fabrication (1).Artificial water channels, bioinspired analogs of AQPs created using synthetic chemistry (19), ideally have a structure that forms a water-permeable channel in the center and an outer surface that is compatible with a lipid membrane environment (1). Interest in artificial water channels has grown in recent years, following decades of research and focus on synthetic ion channels (19). However, two fundamental questions remain: (i) Can artificial channels approach the permeability and selectivity of AQP water chan...

Rectifying nanopores feature ion currents that are higher for voltages of one polarity compared to the currents recorded for corresponding voltages of the opposite polarity. Rectification of nanopores has been found to depend on the pore opening diameter and distribution of surface charges on the pore walls as well as pore geometry. Very little is known, however, on the dependence of ionic rectification on the type of transported ions of the same charge. We performed experiments with single conically shaped nanopores in a polymer film and recorded current–voltage curves in three electrolytes: LiCl, NaCl, and KCl. Rectification degrees of the pores, quantified as the ratio of currents recorded for voltages of opposite polarities, were the highest for KCl and the lowest for LiCl. The experimental observations could not be explained by a continuum modeling based on the Poisson–Nernst–Planck equations. All-atom molecular dynamics simulations revealed differential binding between Li+, Na+, and K+ ions and carboxyl groups on the pore walls, resulting in changes to both the effective surface charge of the nanopore and cation mobility within the pore.

Monodispersed angstrom-size pores embedded in a suitable matrix are promising for highly selective membrane-based separations. They can provide substantial energy savings in water treatment and small molecule bioseparations. Such pores present as membrane proteins (chiefly aquaporin-based) are commonplace in biological membranes but difficult to implement in synthetic industrial membranes and have modest selectivity without tunable selectivity. Here we present PoreDesigner, a design workflow to redesign the robust beta-barrel Outer Membrane Protein F as a scaffold to access three specific pore designs that exclude solutes larger than sucrose (>360 Da), glucose (>180 Da), and salt (>58 Da) respectively. PoreDesigner also enables us to design any specified pore size (spanning 3–10 Å), engineer its pore profile, and chemistry. These redesigned pores may be ideal for conducting sub-nm aqueous separations with permeabilities exceeding those of classical biological water channels, aquaporins, by more than an order of magnitude at over 10 billion water molecules per channel per second.

The motion of polarizable particles in a non-uniform electric field, i.e., dielectrophoresis, has been extensively used for concentration, separation, sorting, and transport of biological particles, from cancer cells and viruses to biomolecules such as DNAs and proteins. However, current approaches to dielectrophoretic manipulation are not sensitive enough to selectively target individual molecular species. Here we describe the application of the dielectrophoretic principle for selective detection of DNA and RNA molecules using an engineered biological nanopore. The key element of our approach is a synthetic polycationic nanocarrier that selectively binds to the target biomolecules, dramatically increasing their dielectrophoretic response to the electric field gradient generated by the nanopore. The dielectrophoretic capture of the nanocarrier-target complexes is detected as a transient blockade of the nanopore ionic current while any non-target nucleic acids are repelled from the nanopore by electrophoresis and thus do not interfere with the signal produced by the target’s capture. Strikingly, we show that even modestly charged nanocarriers can be used to capture DNA or RNA molecules of any length or secondary structure and simultaneously detect several molecular targets. Such selective, multiplex molecular detection technology would be highly desirable for real-time analysis of complex clinical samples.

Aquaporin (AQP) proteins function as highly efficient water transport channels that support homeostasis in many types of living cells. Their structure−function relationships have been characterized extensively in fundamental and applied research, primarily via structural analysis, mutational studies, and computational approaches. The present study evaluates the effects of progressive truncations on the permeability and ionic conductivity of AQP-1 (bovine). The use of truncations to determine critical features has not been considered previously, as physical truncation of AQP is likely not technically feasible due to the ornate arrangement of six interwoven alpha helices in a single pore structure. However, structures not obtainable through protein assembly can be realized via synthetic chemistry approaches and studied using molecular dynamics (MD) simulations. Here, we apply the MD method to characterize the permeability of AQP variants truncated along the pore axis from both cytoplasmic and extracellular sides of the channel. The simulation results suggest that AQP-1 can retain its function even after deletion of up to 50% of the channel's length, representing 50% of proteins' molecular mass. Deletions such as these are expected to greatly simplify future biomimicry efforts of reproducing the AQP functionality using synthetic macromolecules. This study demonstrates the potential of in silico approaches to support the creation of streamlined functional analogues of biological molecular machines.