Aquaporins (AQPs) are biological water channels known for fast water transport (∼10(8)-10(9) molecules/s/channel) with ion exclusion. Few synthetic channels have been designed to mimic this high water permeability, and none reject ions at a significant level. Selective water translocation has previously been shown to depend on water-wires spanning the AQP pore that reverse their orientation, combined with correlated channel motions. No quantitative correlation between the dipolar orientation of the water-wires and their effects on water and proton translocation has been reported. Here, we use complementary X-ray structural data, bilayer transport experiments, and molecular dynamics (MD) simulations to gain key insights and quantify transport. We report artificial imidazole-quartet water channels with 2.6 Å pores, similar to AQP channels, that encapsulate oriented dipolar water-wires in a confined chiral conduit. These channels are able to transport ∼10(6) water molecules/s, which is within 2 orders of magnitude of AQPs' rates, and reject all ions except protons. The proton conductance is high (∼5 H(+)/s/channel) and approximately half that of the M2 proton channel at neutral pH. Chirality is a key feature influencing channel efficiency.

Chiral dipolar oriented water wires are observed inside artificial water channels embedded in supported bilayer membranes.

The amount of inflammatory cytokines is a major determinant for the development of sepsis in very-low-birth-weight (VLBW) neonates. We investigated whether variants of tumor necrosis factor-α, interleukin (IL)-1β, IL-4 receptor α-chain, IL-6 and IL-10 genes, associated with altered cytokine production, might influence the risk and complications of sepsis in VLBW infants. We determined the presence of these genetic variants in dried blood samples of 33 septic, 35 infected and 35 healthy VLBW neonates by PCR and RFLP methods and analyzed their association with the risk and complications of sepsis. The frequencies of genetic variants did not differ in uninfected and in infected infants with or without sepsis. Moreover, none of the studied complications was associated with carrier state of any of genetic variants. Four of the 5 septic neonates with disseminated intravascular coagulation, however, carried simultaneously the variants of IL-1β and IL-10 genes. We concluded that these genetic polymorphisms do not influence the risk and course of sepsis in VLBW neonates.

Triarylamine molecules appended with crown-ethers or carboxylic moieties form self-assembled supramolecular channels within lipid bilayers. Fluorescence assays and voltage clamp studies reveal that the self-assemblies incorporating the crown ethers work as single channels for the selective transport of K or Rb. The X-ray crystallographic structures confirm the mutual columnar self-assembly of triarylamines and crown-ethers. The dimensional fit of K cations within the 18-crown-6 leads to a partial dehydration and to the formation of alternating K cation-water wires within the channel. This original type of organization may be regarded as a biomimetic alternative of columnar K-water wires observed for the natural KcsA channel. Supramolecular columnar arrangement was also shown for the triarylamine-carboxylic acid conjugate. In this latter case, stopped-flow light scattering analysis reveals the transport of water across lipid bilayer membranes with a relative water permeability as high as 17 μm s.

The natural KcsA K channel, one of the best-characterized biological pore structures, conducts K cations at high rates while excluding Na cations. The KcsA K channel is of primordial inspiration for the design of artificial channels. Important progress in improving conduction activity and K /Na selectivity has been achieved with artificial ion-channel systems. However, simple artificial systems exhibiting K /Na selectivity and mimicking the biofunctions of the KcsA K channel are unknown. Herein, an artificial ion channel formed by H-bonded stacks of squalyl crown ethers, in which K conduction is highly preferred to Na conduction, is reported. The K -channel behavior is interpreted as arising from discreet stacks of dimers resulting in the formation of oligomeric channels, in which transport of cations occurs through macrocycles mixed with dimeric carriers undergoing dynamic exchange within the bilayer membrane. The present highly K -selective macrocyclic channel can be regarded as a biomimetic alternative to the KcsA channel.

Artificial water channels-AWCs are known to selectively transport water, with ion exclusion. Similar to natural porins, AWCs encapsulate water wires or clusters, offering continuous and iterative H-bonding that play a vital role in their stabilization. Herein, we report octyl-ureido-polyol AWCs capable of self-assembly into hydrophilic hydroxy-channels. Variants of ethanol, propanediol and trimethanol are used as headgroups to modulate water transport permeabilities, with complete rejection of ions. The hydroxy-channels achieve a single-channel permeability of 2.33 × 10 8 water molecules per second, which is within the same order of magnitude as the transport rates for Aquaporins. Depending on their concentration in the membrane, adaptive channels are observed in the membrane. Over increased concentrations, a significant shift occurs initiating unexpected higher water permeation. Molecular simulations probe that sponge-like or cylindrical aggregates can form to generate transient cluster water pathways through the bilayer. Altogether, the adaptive self-assembly is a key feature influencing channel efficiency The adaptive channels described here may be considered as an important milestone contributing to the systematic discovery of artificial water channels for water desalination.

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