Nature provides a huge range of biological materials, just as ion channels, with various smart functions over millions of years of evolution, and which serve as a big source of bio-inspiration for biomimetic materials. In this critical review, a strategy for the design and synthesis of biomimetic smart nanopores and nanochannels is presented and put into context with recent progress in this rapidly growing field from biological, inorganic, organic to composite nanopore and nanochannel materials, which can respond to single/multiple external stimuli, e.g., pH, temperature, light, and so on. This review is intended to utilize a specific responsive behavior for regulating ionic transport properties inside the single nanopore or nanochannel as an example to demonstrate the feasibility of the design strategy, and provide an overview of this fascinating research field (109 references).

Living organisms make extensive use of micro-and nanometer-sized pores as gatekeepers for controlling the movement of fluids, vapors and solids between complex environments. The ability of such pores to coordinate multiphase transport, in a highly selective and subtly triggered fashion and without clogging, has inspired interest in synthetic gated pores for applications ranging from fluid processing to 3D printing and labon-chip systems 1,2,3,4,5,6,7,8,9,10 . But although specific gating and transport behaviors have been realized by precisely tailoring pore surface chemistries and pore geometries 6,11-17 , a single system capable of selectively handling and controlling complex multiphase transport has remained a distant prospect, and fouling is nearly inevitable 11,12 . Here, we introduce a gating mechanism that uses a capillary-stabilized fluid to seal pores in the closed state, and reversibly and rapidly reconfigures it under pressure to create a non-fouling, fluid-lined pore in the open state. Theoretical modeling and experiments demonstrate that for each transport substance, the gating threshold -the pressure needed to open pores -can be rationally tuned over a wide pressure range. This allows us to realize in one system differential response profiles for a variety of liquids and gases, even letting liquids flow through the pore while preventing gas escape. These capabilities allow us to dynamically modulate gas/liquid sorting in a microfluidic flow and to separate a three-phase air/water/oil mixture, with the fluid lining ensuring sustained antifouling behavior. Because the liquid gating strategy enables efficient long-term operation and can be applied to a variety of pore structures, membrane materials and micro-as well as macro-scale fluid systems, we expect it to prove useful in a wide range of applications.Our hypothesis that a liquid-filled pore could provide a unified gating strategy derives from the idea that a liquid stabilized inside a micropore offers a unique combination of dynamic and interfacial behaviors, and is inspired by nature's use of fluids as reconfigurable gates. Microscale stomata and xylem control air, water, and microbe exchange in plants by using fluid to mechanically reconfigure the pore 18 . The nuclear pore is directly lined with disordered fluidlike proteins that have been proposed not only to regulate differential transport of a wide range of cargos, but also to completely prevent fouling 19 . Most interestingly, micropores between air sacs in the lung are filled with liquid that has been proposed to reversibly reconfigure into an open, fluid-lined pore in response to pressure gradients 20 . Figure 1 contrasts the gating mechanisms in a traditional and in a liquid-filled pore. In the case of traditional nano/micropores (Fig.1a), gases will flow through passively regardless of 2 pore shape and surface chemistry, while liquids will enter the pore once the applied pressure reaches a critical value dictated by the balance of surface interactions, pore geometry and surface tension....

Switchable ion channels that are made of membrane proteins play different roles in cellular circuits. Since gating nanopore channels made of proteins can only work in the environment of lipid membrane, they are not fully compatible to the application requirement as a component of those nanodevice systems in which lipid membranes are hard to establish. Here we report a synthetic nanopore-DNA system where single solid-state conical nanopores can be reversibly gated by switching DNA motors immobilized inside the nanopores. High- (on-state) and low- (off-state) conductance states were found within this nanopore-DNA system corresponding to the single-stranded and i-motif structures of the attached DNA motors. The highest gating efficiency indicated as current ratio of on-state versus off-state was found when the length of the attached DNA molecule matched the tip diameter of the nanopore well. This novel nanopore-DNA system, which was gated by collective folding of structured DNA molecules responding to the external stimulus, provided an artificial counterpart of switchable protein-made nanopore channels. The concept of this DNA motor-driven nanopore switch can be used to build novel, biologically inspired nanopore machines with more precisely controlled functions in the near future by replacing the DNA molecules with other functional biomolecules, such as polypeptides or protein enzymes.

Potassium is especially crucial in modulating the activity of muscles and nerves whose cells have specialized ion channels for transporting potassium. Normal body function extremely depends on the regulation of potassium concentrations inside the ion channels within a certain range. For life science, undoubtedly, it is significant and challenging to study and imitate these processes happening in living organisms with a convenient artificial system. Here we report a novel biomimetic nanochannel system which has an ion concentration effect that provides a nonlinear response to potassium ion at the concentration ranging from 0 to 1500 microM. This new phenomenon is caused by the G-quadruplex DNA conformational change with a positive correlation with ion concentration. In this work, G-quadruplex DNA was immobilized onto a synthetic nanopore, which undergoes a potassium-responsive conformational change and then induces the change in the effective pore size. The responsive ability of this system can be regulated by the stability of G-quadruplex structure through adjusting potassium concentration. The situation of the grafting G-quadruplex DNA on a single nanopore can closely imitate the in vivo condition because the G-rich telomere overhang is attached to the chromosome. Therefore, this artificial system could promote a potential to conveniently study biomolecule conformational change in confined space by the current measurement, which is significantly different from the nanopore sequencing. Moreover, such a system may also potentially spark further experimental and theoretical efforts to simulate the process of ion transport in living organisms and can be further generalized to other more complicated functional molecules for the exploitation of novel bioinspired intelligent nanopore machines.

Bioinspired artificial functional nanochannels for intelligent molecular and ionic transport control at the nanoscale have wide potential applications in nanofluidics, energy conversion, and biosensors. Although various smart passive ion transport properties of ion channels have been artificially realized, it is still hugely challenging to achieve high level intelligent ion transport features in biological ion pumps. Here we show a unique bioinspired single ion pump based on a cooperative pH response double-gate nanochannel, whose gates could be opened and closed alternately/simultaneously under symmetric/asymmetric pH environments. With the stimulation of the double-gate nanochannel by continuous switching of the symmetric/asymmetric pH stimuli, the bioinspired system systematically realized three key ionic transport features of biological ion pumps, including an alternating gates ion pumping process under symmetric pH stimuli, transformation of the ion pump into an ion channel under asymmetric pH stimuli, and a fail-safe ion pumping feature under both symmetric and asymmetric pH stimuli. The ion pumping processes could well be reproduced under a concentration gradient. With the advantages of the extraordinary ionic transport functions of biological ion pumps, the bioinspired ion pump should find widespread applicability in active transportation-controlling smart nanofluidic devices, efficient energy conversions, and seawater desalinization, and open the way to design and develop novel bioinspired intelligent artificial nanochannel materials.

Artificial single nanochannels have emerged as possible candidates for mimicking the process of ionic transport in ion channels and boosting the development of bioinspired intelligent nanomachines for real-world applications, such as biosensors, molecular filtration, and nanofluidic devices. One challenge that remains is to make the artificial nanochannel "smart", with various functions like an organism in Nature. The components of ion channels are asymmetrically distributed between membrane surfaces, which are significant for the implementation of the complex biological function. Inspired by this natural asymmetrical design, here we develop a biomimetic asymmetric responsive single nanochannel system that displays the advanced feature of providing control over pH- and temperature-tunable asymmetric ionic transport properties through asymmetric modifications inside the single nanochannels, which could be considered as a primal platform for the simulation of different ionic transport processes as well as the enhancement of the functionality of ion channels.

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Despite advances in the bioprinting technology, biofabrication of circumferentially multilayered tubular tissues or organs with cellular heterogeneity, such as blood vessels, trachea, intestine, colon, ureter, and urethra, remains a challenge. Herein, a promising multichannel coaxial extrusion system (MCCES) for microfluidic bioprinting of circumferentially multilayered tubular tissues in a single step, using customized bioinks constituting gelatin methacryloyl, alginate, and eight-arm poly(ethylene glycol) acrylate with a tripentaerythritol core, is presented. These perfusable cannular constructs can be continuously tuned up from monolayer to triple layers at regular intervals across the length of a bioprinted tube. Using customized bioink and MCCES, bioprinting of several tubular tissue constructs using relevant cell types with adequate biofunctionality including cell viability, proliferation, and differentiation is demonstrated. Specifically, cannular urothelial tissue constructs are bioprinted, using human urothelial cells and human bladder smooth muscle cells, as well as vascular tissue constructs, using human umbilical vein endothelial cells and human smooth muscle cells. These bioprinted cannular tissues can be actively perfused with fluids and nutrients to promote growth and proliferation of the embedded cell types. The fabrication of such tunable and perfusable circumferentially multilayered tissues represents a fundamental step toward creating human cannular tissues.