Biological Channels Research Articles

Driving Force of Molecular/Ionic Superfluid Formation

Driving Force of Molecular/Ionic Superfluid Formation

Parabolic-elliptic system modeling biological ion channels

The mathematical model of the transport and diffusion of ions in biological channels is considered. It is described by the three-dimensional nonlinear evolution classical Poisson–Nernst–Planck (cPNP) system of partial differential equations with nonlinear coupled boundary conditions. In particular the Chang–Jaffé (CJ) conditions are given on the input and output of a channel. The Robin boundary conditions on a potential are taken. Theorems on the existence, uniqueness and nonnegativity of local weak solutions, in the suitable Sobolev spaces, are proved. The main tool used in the proof of the existence result is the Schauder–Tychonoff fixed point theorem.

Efficient, Positive, and Energy Stable Schemes for Multi-D Poisson–Nernst–Planck Systems

In this paper, we design, analyze, and numerically validate positive and energy-dissipating schemes for solving the time-dependent multi-dimensional system of Poisson–Nernst–Planck equations, which has found much use in the modeling of biological membrane channels and semiconductor devices. The semi-implicit time discretization based on a reformulation of the system gives a well-posed elliptic system, which is shown to preserve solution positivity for arbitrary time steps. The first order (in time) fully-discrete scheme is shown to preserve solution positivity and mass conservation unconditionally, and energy dissipation with only a mild O(1) time step restriction. The scheme is also shown to preserve the steady-states. For the fully second order (in both time and space) scheme with large time steps, solution positivity is restored by a local scaling limiter, which is shown to maintain the spatial accuracy. These schemes are easy to implement. Several three-dimensional numerical examples verify our theoretical findings and demonstrate the accuracy, efficiency, and robustness of the proposed schemes, as well as the fast approach to steady-states.

Aquaporin 1 and 3 as local vitality markers in mechanical and thermal skin injuries

Assessment of the vitality of an injury is one of to the main tasks in daily forensic casework. Aquaporins belong to the family of water channels. They enable the transport of water and of small molecules like glycerol through biological channels. So far, 13 classes of aquaporins are identified in vertebrates. The classical aquaporin channels 1, 2 and 4 are only permeable for water. The aquaporin channels 3, 7, 9 and 10 are also called aquaglycerolporins since they can also transport glycerol. Aquaporin 3 is expressed in epidermal keratinocytes. In the present investigation, the aquaporin 1 and 3 expression in mechanically and thermally damaged skin is investigated by immunohistochemistry. The study collective comprises 30 cases (63.3% male and 36.7% female) with an age range between 19 and 95 years (mean value 54.6 years). The skin injury comprises different kinds of blunt force, sharp force, strangulation marks, thermal injury, gunshot wounds and frost erythema. In all kinds of mechanical and trauma injury, an increased expression of aquaporin 3 in the keratinocytes of the epidermis was found. There is no correlation of the aquaporin 3 expression with age, sex, body mass index, duration of agonal period and postmortem interval. Concerning aquaporin 1, there were no differences between injured and uninjured skin. Aquaporin 3 is independently from the kind of skin injury and appears to be a valuable immunohistochemical parameter of vitality.

Water transport performance of inhomgenous nanoconfined systems

Graphene nanochannels have attracted extensive attention in the fields of physics, biology, mechanics and materials due to their super long slip length and unique fluid transport properties. Up to now, research on confined liquid transport of carbon-based materials relies primarily on homogeneous nanoconfinement. Here, we investigate the transport behavior of confined water between inhomogeneous graphene channels by means of molecular dynamics simulations. Our results show that the confined water in the channel transforms into different lamellar structures in different areas. With the increase of water density, the water structure will gradually change from liquid to regular square-like solid. Besides, the speed of water decreases first, then increases and then decreases again with the increase of water density. This is because under low density (0.8–0.9 g/cm3), the interface friction increases with the increase of density, causing the speed of water to decrease. When the density reaches phase transition density (1.0 g/cm3), the friction coefficient will reduce sharply. With the continuing increase of density (1.0–1.4 g/cm3), interface friction increases, leading to speed drop of water again. Our results provide theoretical support for understanding the phase state and transport characteristics of water in confined systems, and have some guiding significance for material transport in biological channels and seawater desalination.

Engineering a Smart Nanofluidic Sensor for High-Performance Peroxynitrite Sensing through a Spirocyclic Ring Open/Close Reaction Strategy.

Peroxynitrite (ONOO-) is an important reactive oxygen/nitrogen species that participates in a range of physiological and pathological processes by modulating ion flux through biological channels. Inspired by a ONOO--regulated K+ channel in vivo, herein, we describe the construction of a smart ONOO--driven nanosensor using a spirocyclic ring open/close reaction approach. The prepared nanosensor possessed a prominent ONOO- selectivity and sensitivity and rapid response (∼90 s) owing to the specific reaction between ONOO- and ligands on the nanosensor surface with a high ion rectification ratio (∼10) and ion gating ratio (∼4). Moreover, this nanosensor system also exhibits excellent stability and recyclability. Thus, these results will provide a new direction for the design of nanochannel-based sensors for future practical and biological applications.

Artificial channels for confined mass transport at the sub-nanometre scale

Mass transport at the sub-nanometre scale, including selective transport of gases, liquids and ions, plays a key role in systems such as catalysis, energy generation and storage, chemical sensing and molecular separation. Highly efficient biological channels in living organisms have inspired the design of artificial channels with similar, or even higher, mass-transport efficiency, which can be used at a much larger scale. In this Review, we highlight synthetic-nanomaterials-enabled channels in the platforms of well-defined nanopores, 1D nanotubes and 2D nanochannels, and discuss their design principles, channel architectures and membrane or device fabrication. We focus on fundamental mechanisms of sub-nanometre confined mass transport and their relationships with the structure–property–performance. We then present the practicalities of these channels and discuss their potential impact on the development of next-generation sustainable technologies for use in applications related to energy, the environment and healthcare. Artificial channels that selectively transport small molecules at the sub-nanometre scale are used in many applications, but, in particular, in molecular separation. This Review discusses the design of channels, nanostructure, fabrication and mass-transport mechanisms, as well as outlining promising applications and the challenges ahead.

Bioinspired artificial nanochannels: construction and application

Inspired by nature, this review focuses on the construction and applications of biomimetic artificial nanochannels from the perspective of the relationship between biological channels and artificial nanochannels.

Maternal Undernutrition in Adolescence and Child Human Capital Formation over the Life-Course: Evidence from an International Cohort Study

Adolescence has been highlighted as a period when environments are critical for the human capital development of women, and thus of their children, but evidence on this from low- and middle-income countries is scarce. We estimate the effect of mother adolescent undernutrition on offspring growth and development from infancy through adolescence using data from Ethiopia, India, Peru, and Vietnam and Instrumental Variables (IV) estimation that employs rainfall shocks during mother’s adolescence as instruments for mother’s nutritional status. We find a positive and significant effect of mother adolescent nutritional status on child height-for-age in infancy that persists through to adolescence and evidence that this may manifest mainly through a biological channel. Our results also support a significant impact of rainfall shocks during mother’s early adolescence on mother’s adult height and child growth from infancy to adolescence. We find no significant effect of mother’s adolescent nutritional status and rainfall shocks during mother’s adolescence on child achievement tests scores, however.

Monolithic Biochar-Supported Cobalt-Based Catalysts with High-Activity and Superior-Stability for Biomass Tar Reforming

In this paper, monolithic biochar-supported cobalt-based catalysts with unique long and through mesopores were synthesized based on the biological channels of biomass materials through simple impregnation and carbonization and evaluated in a biomass tar model (toluene) steam reforming and biomass pyrolysis tar decomposition reactions. Regular channels with a diameter of around 20-40 μm are well retained after carbonization for the monolithic biochar. Co0, Co-Fe and Co-Ni alloy nanoparticles are formed and dispersed uniformly on the surface of the channels of catalyst PC@Co2, PC@Co1Fe1, and PC@Co1Ni1, which are anchored firmly by graphitic carbon layer. At 700 oC, the carbon deposition resistance of PC@Co1Fe1 and PC@Co1Ni1 was significantly improved due to the introduction of the Fe and Ni, and excellent performance were achieved during the 360 min continuous toluene reforming experiments. The average toluene reforming rate reached around 97 % and 85.3% by using PC@Co1Ni1 and PC@Co1Fe1 as the catalysts, and H2 and CO were the main product with a small amount of CO2 and CH4. PC@Co1Ni1 also showed high activity in the decomposition of biomass pyrolysis tar with a high average tar conversion efficiency of around 91% and excellent stability in a five-cycle test, and H2 yield was also significantly improved.

The Bionic Water Channel of Ultra-Short, High Affinity Carbon Nanotubes with High Water Permeability and Proton Selectivity

The development of the bionic water channel aims to replace the possible use of natural aquaporins (AQPs) for water purification, while retaining the ability of natural AQPs to carry out ultra-fast water transport and repel ions. Carbon nanotube channels (CNTCs) are a convenient membrane-based model system for studying nano-fluidic transport that replicates a number of key structural features of biological membrane channels. In this report, we describe protocols for CNTCs synthesis by ultrasound-assisted cutting of long CNTs in the presence of lipid amphiphiles. CNTCs have a similar thickness to the lipid membrane and high affinity for it. The ultra-short high-affinity CNTCs have high permeability and ion selectivity. The water permeability of the CNTCs is 1936 ± 123 μm/s, which is 2.3 times that of natural AQPs, and completely rejects salt ions. In general, carbon nanotubes represent a multifunctional nanopore building module for creating high-ranking functional bionic materials. This study has reference significance for the design of new bionic water channel and the actual development of bionic membrane based on CNTs.

High-speed super-resolution imaging of rotationally symmetric structures using SPEED microscopy and 2D-to-3D transformation.

Various super-resolution imaging techniques have been developed to break the diffraction-limited resolution of light microscopy. However, it still remains challenging to obtain three-dimensional (3D) super-resolution information of structures and dynamic processes in live cells at high speed. We recently developed high-speed single-point edge-excitation sub-diffraction (SPEED) microscopy and its two-dimensional (2D)-to-3D transformation algorithm to provide an effective approach to achieving 3D sub-diffraction-limit information in subcellular structures and organelles that have rotational symmetry. In contrast to most other 3D super-resolution microscopy or 3D particle-tracking microscopy approaches, SPEED microscopy does not depend on complex optical components and can be implemented onto a standard inverted epifluorescence microscope. SPEED microscopy is specifically designed to obtain 2D spatial locations of individual immobile or moving fluorescent molecules inside sub-micrometer biological channels or cavities at high spatiotemporal resolution. After data collection, post-localization 2D-to-3D transformation is applied to obtain 3D super-resolution structural and dynamic information. The complete protocol, including cell culture and sample preparation (6-7 d), SPEED imaging (4-5 h), data analysis and validation through simulation (5-13 h), takes ~9 d to complete.

Polydisperse molecular architecture of connexin 26/30 heteromeric hemichannels revealed by atomic force microscopy imaging

Connexin (Cx) protein forms hemichannels and gap junctional channels, which play diverse and profound roles in human physiology and diseases. Gap junctions are arrays of intercellular channels formed by the docking of two hemichannels from adjacent cells. Each hexameric hemichannel contains the same or different Cx isoform. Although homomeric Cxs forms have been largely described functionally and structurally, the stoichiometry and arrangement of heteromeric Cx channels remain unknown. The latter, however, are widely expressed in human tissues and variation might have important implications on channel function. Investigating properties of heteromeric Cx channels is challenging considering the high number of potential subunit arrangements and stoichiometries, even when only combining two Cx isoforms. To tackle this problem, we engineered an HA tag onto Cx26 or Cx30 subunits and imaged hemichannels that were liganded by Fab-epitope antibody fragments via atomic force microscopy. For Cx26-HA/Cx30 or Cx30-HA/Cx26 heteromeric channels, the Fab-HA binding distribution was binomial with a maximum of three Fab-HA bound. Furthermore, imaged Cx26/Cx30-HA triple liganded by Fab-HA showed multiple arrangements that can be derived from the law of total probabilities. Atomic force microscopy imaging of ringlike structures of Cx26/Cx30-HA hemichannels confirmed these findings and also detected a polydisperse distribution of stoichiometries. Our results indicate a dominant subunit stoichiometry of 3Cx26:3Cx30 with the most abundant subunit arrangement of Cx26-Cx26-Cx30-Cx26-Cx30-Cx30. To our knowledge, this is the first time that the molecular architecture of heteromeric Cx channels has been revealed, thus providing the basis to explore the functional effect of these channels in biology.

Construction of a Smart Nanofluidic Sensor through a Redox Reaction Strategy for High-Performance Carbon Monoxide Sensing.

Carbon monoxide (CO), an important gas signaling molecule, demonstrated various physiological and pathological functions by regulating the ion flux of biological channels. Herein, inspired by the CO-regulated K+ channel in vivo, we propose a smart CO-responsive nanosensor through the redox reaction strategy. Such nanosensor demonstrated an outstanding CO specificity and selectivity with high ion rectification (∼9) as well as excellent stability and recyclability. Therefore, these results will provide a new direction for the design of nanochannel-based sensors for future practical and biological applications.

Hydrophobic dewetting in gating and regulation of transmembrane protein ion channels.

Water is at the heart of almost all biological phenomena, without which no life that we know of would have been possible. It is a misleadingly complex liquid that exists in near coexistence with the vapor phase under ambient conditions. Confinement within a hydrophobic cavity can tip this balance enough to drive a cooperative dewetting transition. For a nanometer-scale pore, the dewetting transition leads to a stable dry state that is physically open but impermeable to ions. This phenomenon is often referred to as hydrophobic gating. Numerous transmembrane protein ion channels have now been observed to utilize hydrophobic gating in their activation and regulation. Here, we review recent theoretical, simulation, and experimental studies that together have started to establish the principles of hydrophobic gating and discuss how channels of various sizes, topologies, and biological functions can utilize these principles to control the thermodynamic properties of water within their interior pores for gating and regulation. Exciting opportunities remain in multiple areas, particularly on direct experimental detection of hydrophobic dewetting in biological channels and on understanding how the cell may control the hydrophobic gating in regulation of ion channels.

Molecular Transport through a Biomimetic DNA Channel on Live Cell Membranes.

Biological membrane channels, considered as molecular gatekeepers, control the transportation of molecules and ions across live cell membranes. Developing synthetic passable channels with predictable structures, high transport efficiency, and low cytotoxicity on live cells is of great interest for replicating the functions of endogenous protein channels, but remains challenging. The development of DNA nanotechnology provides possible solutions for making synthetic channels with precise structures and controllable functionalization. Therefore, in this work, we constructed a phosphorothioate-modified DNA nanopore able to structurally mimic biological channels for molecular transport across live cell membranes. With its stable structure with small hollow size (<2 nm) and the ability to interact with the lipid molecules, this DNA nanopore could show stable insertion into the plasma membrane. We further proved that this membrane-spanning channel could transport ions and antitumor drugs to neurons and cancer cells, respectively, and do so within a certain time window. We expect that this live cell membrane-spanning synthetic DNA nanopore will provide a tool for studying cellular communication, building synthetic cells, and achieving controlled transmembrane transport to cells.

Water in Nanopores and Biological Channels: A Molecular Simulation Perspective.

This Review explores the dynamic behavior of water within nanopores and biological channels in lipid bilayer membranes. We focus on molecular simulation studies, alongside selected structural and other experimental investigations. Structures of biological nanopores and channels are reviewed, emphasizing those high-resolution crystal structures, which reveal water molecules within the transmembrane pores, which can be used to aid the interpretation of simulation studies. Different levels of molecular simulations of water within nanopores are described, with a focus on molecular dynamics (MD). In particular, models of water for MD simulations are discussed in detail to provide an evaluation of their use in simulations of water in nanopores. Simulation studies of the behavior of water in idealized models of nanopores have revealed aspects of the organization and dynamics of nanoconfined water, including wetting/dewetting in narrow hydrophobic nanopores. A survey of simulation studies in a range of nonbiological nanopores is presented, including carbon nanotubes, synthetic nanopores, model peptide nanopores, track-etched nanopores in polymer membranes, and hydroxylated and functionalized nanoporous silica. These reveal a complex relationship between pore size/geometry, the nature of the pore lining, and rates of water transport. Wider nanopores with hydrophobic linings favor water flow whereas narrower hydrophobic pores may show dewetting. Simulation studies over the past decade of the behavior of water in a range of biological nanopores are described, including porins and β-barrel protein nanopores, aquaporins and related polar solute pores, and a number of different classes of ion channels. Water is shown to play a key role in proton transport in biological channels and in hydrophobic gating of ion channels. An overall picture emerges, whereby the behavior of water in a nanopore may be predicted as a function of its hydrophobicity and radius. This informs our understanding of the functions of diverse channel structures and will aid the design of novel nanopores. Thus, our current level of understanding allows for the design of a nanopore which promotes wetting over dewetting or vice versa. However, to design a novel nanopore, which enables fast, selective, and gated flow of water de novo would remain challenging, suggesting a need for further detailed simulations alongside experimental evaluation of more complex nanopore systems.

Stochastic Ionic Transport in Single Atomic Zero-Dimensional Pores.

We report on single atomic zero-dimensional (0D) pores fabricated using aberration-corrected scanning transmission electron microscopy (AC-STEM) in monolayer MoS2. Pores are comprised of a few atoms missing in the two-dimensional (2D) lattice (1-5 Mo atoms) of characteristic sizes from ∼0.5 to 1.2 nm, and pore edges directly probed by AC-STEM to map the atomic structure. We categorize them into ∼30 geometrically possible zigzag, armchair, and mixed configurations. While theoretical studies predict that transport properties of 2D pores in this size range depend strongly on pore size and their atomic configuration, 0D pores show an average conductance in the range from ∼0.6-1 nS (bias up to 0.1 V), similar to biological pores. In some devices, the current was immeasurably small and/or pores could not be wet. Furthermore, current-voltage (I-V) characteristics are largely independent of bulk molarity (10 mM to 3 M KCl) and the type of cation (K+, Li+, Mg2+). This work lays the experimental foundation for understanding of the confinement effects possible in atomic-scale 2D material pores and the realization of solid-state analogues of ion channels in biology.

Voltage-gated multilayer graphene nanochannel for K+/Na+ separation: A molecular dynamics study

Biological protein channels have a series of remarkable properties such as selective ion or water transport. In this work, using molecular dynamics simulations, a bioinspired flexible graphene nanochannel were designed based on the structures and mechanisms of biological K+ channel. The results show that the graphene nanochannel stacked from six graphene nanopores with four carbonyl groups attached at the edges of each pore presents a voltage-gated K+/Na+ separation. As the increase of voltage bias, the separation performance first increases and then decreases. The potential of mean force curves for K+ and Na+ indicate that the energy barrier for K+ transport is smaller due to the easier dehydration of K+, which results in its higher ion current. Meanwhile, the hydration structures of the passing ions under different electric field intensities show that the transport of K+ through dihydrate is more efficient, which leads to the higher separation ratio. In addition, self-driven and Coulomb knock-on ion transport mechanisms are revealed. These findings provided here deepen our understanding about the mechanism of selectively ion transport in biological ion channels, and also give a general scheme for the design of flexible nanochannels that can be used in ion sensors, nanofiltration, and other related voltage-gated nanofluidic devices.

Carbon nanotube porin diffusion in mixed composition supported lipid bilayers

Carbon nanotube porins (CNTPs), short pieces of carbon nanotubes capable of self-inserting into a lipid bilayer, represent a simplified model of biological membrane channels. We have used high-speed atomic force microscopy (HS-AFM) and all-atom molecular dynamics (MD) simulations to study the behavior of CNTPs in a mixed lipid membrane consisting of DOPC lipid with a variable percentage of DMPC lipid added to it. HS-AFM data reveal that the CNTPs undergo diffusive motion in the bilayer plane. Motion trajectories extracted from the HS-AFM movies indicate that CNTPs exhibit diffusion coefficient values broadly similar to values reported for membrane proteins in supported lipid bilayers. The data also indicate that increasing the percentage of DMPC leads to a marked slowing of CNTP diffusion. MD simulations reveal a CNTP-lipid assembly that diffuses in the membrane and show trends that are consistent with the experimental observations.