Advances in Artificial Cell Membrane Systems as a Platform for Reconstituting Ion Channels

An artificial cell membrane that is composed of bilayer lipid membranes (BLMs) with transmembrane proteins incorporated within them represents a well‐defined system for the analysis of membrane proteins, especially ion channel proteins that are major targets for drug design. Because the BLM system has a high compatibility with recently developed cell‐free expression systems, it has attracted attention as a next‐generation drug screening system. However, three issues associated with BLM systems, i. e., their instability, the need for non‐volatile organic solvents and a low efficiency of ion channel incorporation, have limited their use as a drug screening platform. In this personal account, we discuss our recent approaches to address these issues based on microfabrication. We also discuss the potential for using the BLM system combined with cell‐free expression systems as a drug screening system for future personalized medicine.     

Practical considerations for preparing polymerized phospholipid bilayer capillary coatings for protein separations

Phosphorylcholine (PC) based phospholipid bilayers have proven useful as capillary coating materials due to their inherent resistance to non-specific protein adsorption. The primary limitation of this important class of capillary coatings remains the limited long-term chemical and physical stability of the coatings. Recently, a method for increasing phospholipid coating stability in fused silica capillaries via utilization of polymerized, synthetic phospholipids was reported. Here, we expand upon these studies by investigating polymerized lipid bilayer capillary coatings with respect to separation performance including run-to-run, day-to-day and column-to-column reproducibility and long-term stability. In addition, the effects of pH and capillary inner diameter on polymerized phospholipid coated capillaries were investigated to identify optimized coating conditions. The coatings are stabilized for protein separations across a wide range of pH values (4.0–9.3), a unique property for capillary coating materials. Additionally, smaller inner diameter capillaries (≤50 μm) were found to yield marked enhancements in coating stability and reproducibility compared to wider bore capillaries, demonstrating the importance of capillary size for separations employing polymerized phospholipid coatings.     

Biomembrane mimetic electrochemical sensors

Biomimetic approaches to the assembling of regular layers of electrochemical sensors make it possible to extend their performance because of the tuning shape and charge of the lipid analogs and implementation of artificial receptors in the lipid layers. The role of artificial components in modification of the properties of the surface layers and application of the nanopore devices are of particular interest. In review, recent trends in assembling modified lipid membranes and their artificial analogs with nanopores have been considered with particular emphasis on their use in electrochemical sensors.     

Tunable bandgaps and flat bands in twisted bilayer biphenylene carbon

Owing to the interaction between the layers, the twisted bilayer two-dimensional(2 D) materials exhibit numerous unique optical and electronic properties different from the monolayer counterpart, and have attracted tremendous interests in current physical research community. By means of first-principles and tight-binding model calculations, the electronic properties of twisted bilayer biphenylene carbon(BPC) are systematically investigated in this paper. The results indicate that the effect of twist will not only leads to a phase transition from semiconductor to metal, but also an adjustable band gap in BPC(0 me V to 120 me V depending on the twist angle). Moreover, unlike the twisted bilayer graphene(TBG), the flat bands in twisted BPC are no longer restricted by "magic angles", i.e., abnormal flat bands could be appeared as well at several specific large angles in addition to the small angles. The charge density of these flat bands possesses different local modes, indicating that they might be derived from different stacked modes and host different properties. The exotic physical properties presented in this work foreshow twisted BPC a promising material for the application of terahertz and infrared photodetectors and the exploration of strong correlation.     

Room Temperature Ferromagnetism in Graphene/SiC(0001) System Intercalated by Fe and Co

The utilization of graphene on silicon carbide (SiC) substrates holds substantial promise for advancements in spintronics and nanoelectronics. Furthermore, incorporating magnetic metals provides an optimal framework for probing fundamental physical phenomena. The approach to developing such systems is in situ intercalation of graphene with magnetic metals. Herein, the electronic structure is analyzed and the magnetic properties of the system are synthesized by the thermal decomposition of 6H-SiC(0001) surface and subsequent intercalation of graphene with cobalt (Co) and iron (Fe) atoms. X-ray photoemission spectroscopy and low-energy electron diffraction are employed to control the synthesis and metal intercalation processes. The morphological characteristics of the synthesized system are studied by means of atomic force microscopy. The findings derived from magneto-optic Kerr effect measurements reveal a homogeneous ferromagnetic ordering at room temperature. Angle-resolved photoemission spectroscopy is used to ascertain the impact of intercalation on graphene's electronic structure. The results of this study are essential for the development of graphene-based spintronics and nanoelectronic devices as well as for fundamental studies in magnetic graphene systems.     

Combination of the CHARMM27 force field with united-atom lipid force fields

Computer simulations offer a valuable way to study membrane systems, from simple lipid bilayers to large transmembrane protein complexes and lipid-nucleic acid complexes for drug delivery. Their accuracy depends on the quality of the force field parameters used to describe the components of a particular system. We have implemented the widely used CHARMM22 and CHARMM27 force fields in the GROMACS simulation package to (i) combine the CHARMM22 protein force field with two sets of united-atom lipids parameters; (ii) allow comparisons of the lipid CHARMM27 force field with other lipid force fields or lipid-protein force field combinations. Our tests do not show any particular issue with the combination of the all-atom CHARMM22 force field with united-atoms lipid parameters, although pertinent experimental data are lacking to assess the quality of the lipid-protein interactions. The conversion utilities allow automatic generation of GROMACS simulation files with CHARMM nucleic acids and protein parameters and topologies, starting from pdb files using the standard GROMACS pdb2gmx method. CMAP is currently not implemented.     

Membrane-active properties and antiradical activity of gossypol and its derivatives

A novel asymmetric gossypol derivative was synthesized. The antioxidant activity of gossypol and certain of its derivatives at the aldehyde groups and the interaction of these compounds with model membranes were studied. It was shown that the antiradical and membrane activities of the gossypol derivatives were determined by the structure of the substituent and that gossypol and its derivatives were partially localized in the lipid bilayer and possibly induced formation of a new interdigitating phase. Published in Khimiya Prirodnykh Soedinenii, No. 3, pp. 265–266, May–June, 2008.     

Potential Anti-Alzheimer Agents from Guanidinyl Tryptophan Derivatives with Activities of Membrane Adhesion and Conformational Transition Inhibitions

Guanidinyl tryptophan derivatives TGN1, TGN2, TGN3, and TGN4 were synthesized, and these compounds were shown to possess in vitro inhibitory activity for amyloid aggregation in a previous study. Nevertheless, the influence of the TGN series of compounds on the binding and permeation behaviors of an Aβ monomer to the cell membranes was not elucidated. In this study, we investigated the effect of compounds in the TGN series on the behavior of an Aβ monomer regarding its toxicity toward the bilayer lipid membrane using molecular dynamics (MD) simulation. MD simulations suggest that TGN4 is a potential agent that can interfere with the movement of the Aβ monomer into the membrane. The MM-GBSA result demonstrated that TGN4 exhibits the highest affinity to the Aβ_1–42 monomer but has the lowest affinity to the bilayer. Moreover, TGN4 also contributes to a decrease in the binding affinity between the Aβ_1–42 monomer and the POPC membrane. Regarding the results of the binding mode and conformational analyses, a high number of amino-acid residues were shown to provide the binding interactions between TGN4 and the Aβ_1–42 monomer. TGN4 also reduces the conformational transition of the Aβ_1–42 monomer by means of interacting with the monomer. The present study presents molecular-level insights into how the TGN series of compounds affect the membrane adsorption and the conformational transition of the Aβ_1–42 monomer, which could be valuable for the further development of new anti-Alzheimer agents.     

Ion Channel Behavior of a Supported Bilayer Lipid Membrane Composed of 5,5-Ditetradecyl-2-(2-trimethyl-ammonioethyl)-1,3-dioxane Bromide Modified Glassy Carbon Electrode

A synthetic cationic surfactant, 5, 5-ditetradecyl-2-(2-trimethyl-ammonioethyl)-1, 3-dioxane bromide (DTDB), was used toconstruct a supported bilayer lipid membrane (s-BLM) coatedon an underlying glassy carbon electrode (GCE). Electrochem-ical impedance spectroscopy (EIS), small-angle X-ray diffrac-tion (SAXD) and cyclic voltammetry were used to characterizethe s-BLM. Both EIS and SAXD data indicated that the syn-thetic lipid exists as a well-oriented bilayer in the membrane.     

Ionophoric and Complexant Properties of Lagochilin Derivatives

The ionophoric and complexant properties of synthetic derivatives of lagochilin, 3,18-O-isopropylidenelagochilin and 3,18-O-ethylidenelagochilin, were studied by BLM methods, conductometry, and IR spectroscopy. The ionophoric activity was found to be highly selective for divalent cations. Studies of the electrical conductivity of alkaline-earth metal salts in the presence of the lagochilin derivatives and analysis of their IR spectra have shown that they can form complexes with various ratios of metal ions.