Bilayer Interface Research Articles

Signature of Proton-Hole Transfer in Hydrogen-Bonded Solids at 10 K.

Although proton transport in water ice is well understood, proton-hole transfer (PHT) involving proton abstraction by anions remains less explored. This study investigates PHT in H2S and NH3 solids at low temperatures, aiming to determine whether these solids exhibit negative charge transport similar to that in ice. In H2S and NH3 solids at 10 K, surface HS- and NH2- anions in hydrogen-bonded systems trigger negative current flow, providing a clear signature of PHT. This negative current is controlled by electron flow and 193 nm ultraviolet irradiation, which generates HS- and NH2- anions on the solid surfaces. In bilayer H2S/H2O and NH3/H2O solids, a significant negative current is observed only in the NH3/H2O solid, which is attributed to the exothermic proton abstraction by NH2- from H2O at the bilayer interface, a process not available for H2S on ice. This study is the first to demonstrate PHT-induced electrochemical behavior in hydrogen-bonded solids other than ice.

DIB‐BOT: An Open‐Source Hardware Approach for Plate‐Integrated Droplet Interface Bilayer Deposition

AbstractDroplet interface bilayers (DIBs) offer a controlled lipid environment for studying membrane‐bound processes, with applications in artificial cells, biosensing, and biophysics. Current DIB fabrication faces challenges due to time‐consuming processes and specialized equipment, limiting scale‐up and hindering statistical significance in single‐molecule assays. This research introduces “DIB‐BOT,” an open‐source solution combining a nanoinjector and a 3D printer. DIB‐BOT enables rapid, reproducible DIB fabrication, overcoming manual limitations. Using off‐the‐shelf components, DIB‐BOT ensures high spatial reproducibility, minimal user input, and scalable experiments. The system's utility is demonstrated through pairwise droplet assembly and a fluorescence plate‐reader assay. Compared to manual fabrication, DIB‐BOT shows a 10‐fold reduction in droplet volume error, a threefold reduction in positional error, and 100% droplet yield. This method lowers entry barriers to DIB research, expanding its applications and enhancing data quality.

Bilayer interface engineering through 2D/3D perovskite and surface dipole for inverted perovskite solar modules

The persistency of passivation and scalable uniformity are vital issues that limit the improvement of performance and stability of large-area perovskite solar modules (PSMs). Here, we design a bilayer interface engineering strategy that takes advantage of the stability and passivation ability of low-dimensional perovskite and the dipole layer. Introducing phenethylammonium iodide (PEAI) can form 2D/3D heterojunctions on the perovskite surface and effectively passivate defects of perovskite film. Interestingly, the upper piperazinium iodide (PI) layer can still form surface dipoles on the 2D/3D perovskite surface to optimize energy-level alignment. Moreover, the bilayer interface engineering enables large-area perovskite films with uniform surface morphology, lower trap-state density and stability against environmental stress factors. The final devices achieved a small-area PCE of 25.20% and a large-area (1 cm2) PCE of 23.96%. A perovskite mini-module (5 × 5 cm2 with an active area of 14.28 cm2) could also be fabricated to achieve a PCE of 23.19%, ranking it among the highest for inverted PSMs. Additionally, the device could retain over 93% of its initial efficiency after MPP tracking at 45 °C for 1280 hours. This study successfully demonstrates a bilayer interface engineering with respective functions, offering valuable insights for producing efficient and stable large-area PSCs.

Stable driving voltage in exciplex-type OLEDs with a bilayer interface

Organic light-emitting diodes (OLEDs) that produce exciplexes in a bilayer are device structures that can dramatically reduce the turn-on voltage. In this study, we report that this device structure contributes to an impressive improvement in operating lifetime. The lifetime of our OLED is 200 times longer than that of conventional OLEDs, and the voltage does not change after 100 h of operation. The reason for the stable driving voltage is no carrier accumulation inside the device at all by using a displacement current measurement. Analyzing the carrier dynamics in this work will provide a comprehensive solution for OLED degradation.

Interface charge accumulation in bi-layer dielectrics between cable and accessory insulation under temperature gradient

Bi-layer dielectrics are a feature of high-voltage direct-current cable and accessory systems, giving rise to the interfaces between the cable and accessory insulation. The interfaces act as preference sites for space charge build-up and are therefore regarded as potential breakdown initiation sites. A further complication is that during the operation of cable, a temperature gradient (TG) will be produced across the bi-layer insulation. In this paper, carbon black (CB) nanoparticles with 0, 0.5, 1, 1.5, 3.5 and 5.5 wt% are doped into silicon rubber (SR), space charge distributions in bi-layer dielectrics composed of cross-linked polyethylene (XLPE) and CB/SR nanocomposites under DC voltage and TG are measured using the pulsed electroacoustic method, and the effects of the doping proportion of CB nanoparticles and the TG on the bi-layer interface charge behavior are investigated. The experimental results show that under the TG, CB nanoparticles doped into SR can effectively suppress the interface charge accumulation, the amount of the interface charge decreases with the increase of the doping proportion from 0 to 1.5 wt% but increases with the increase of the doping proportion from 1.5 to 5.5 wt%, and the CB nanoparticle with 1.5 wt% shows relatively better suppression effect on the interface charge accumulation. With the increase of the TG, the amount of the interface charge increases initially and then decreases.

Long exciton diffusion distance and efficient exciton dissociation enable high efficiency planar heterojunction non-fullerene organic solar cells

We characterized exciton diffusion and dissociation behaviour in two ITIC derivatives non-fullerene acceptors (NFA) by time-resolved spectroscopic methods. The exciton diffusion length was determined to be ∼26 and ∼34 nm in ITIC and IT4F. We further examined the dissociation of excitons in those NFA at the acceptor/donor planar heterojunction interfaces by transient absorption measurements, in which efficient charge generation was observed. Finally, we fabricated planar heterojunction solar cells using PM6/NFA bilayer planar heterojunctions; a power conversion efficiency (PCE) of over 7 % for PM6/IT4F bilayers was determined. More importantly, the spin-coating of top layer NFA has negligible influence on the morphology of the PM6 layer, suggesting a clear bilayer interface, rather than a quasi-bilayer structure with a portion of bulk heterojunction. The results suggest that enhanced exciton diffusion length and efficient exciton dissociation and charge generation are elemental characters to realize high PCE planar heterojunction organic solar cells. We established direct linking between the exciton diffusion length and the photocurrent generation in NFA layer by transfer matrix simulation. The large exciton diffusion length in NFAs makes the realization of high efficiency and stable bilayer organic solar cells feasible.

Fermi Resonance of the N-D Stretching Mode Probing the Local Hydrogen-Bonding Environment in Proteins.

Local H-bonding interactions are crucial for proteins to undergo various structural transitions and form different secondary structures. However, identifying slight distinctions in the local H-bonding of proteins is rather challenging. Here, we demonstrate that the Fermi resonance of the N-D stretching mode can provide an effective probe for the localized H-bonding environment of proteins both at the surface/interface and in the bulk. Using sum frequency generation vibrational spectroscopy and infrared spectroscopy, we established a correlation between the Fermi resonance of the N-D mode and protein secondary structures. The H-bond of N-D···C═O splits the N-D modes into two peaks (∼2410 and ∼2470 cm-1). The relative strength ratio (R) between the ∼2410 cm-1 peak and the ∼2470 cm-1 peak is very sensitive to H-bond strength and protein secondary structure. R is less than 1 for α-helical peptides, while R is greater than 1 for β-sheet peptides. For R < 2.5, both α-helical/loop structures and β-sheet structures exhibit almost identical Fermi coupling strengths (W = 28 cm-1). For R > 2.5, W decreases from 28 to 14 cm-1 and depends on the aggregation degree of the β-sheet oligomers or fibrils. The initial local H-bonding status impacts the misfolding dynamics of proteins at the lipid bilayer interface.

Manipulation of encapsulated artificial phospholipid membranes using sub-micellar lysolipid concentrations

Droplet Interface Bilayers (DIBs) constitute a commonly used model of artificial membranes for synthetic biology research applications. However, their practical use is often limited by their requirement to be surrounded by oil. Here we demonstrate in-situ bilayer manipulation of submillimeter, hydrogel-encapsulated droplet interface bilayers (eDIBs). Monolithic, Cyclic Olefin Copolymer/Nylon 3D-printed microfluidic devices facilitated the eDIB formation through high-order emulsification. By exposing the eDIB capsules to varying lysophosphatidylcholine (LPC) concentrations, we investigated the interaction of lysolipids with three-dimensional DIB networks. Micellar LPC concentrations triggered the bursting of encapsulated droplet networks, while at lower concentrations the droplet network endured structural changes, precisely affecting the membrane dimensions. This chemically-mediated manipulation of enclosed, 3D-orchestrated membrane mimics, facilitates the exploration of readily accessible compartmentalized artificial cellular machinery. Collectively, the droplet-based construct can pose as a chemically responsive soft material for studying membrane mechanics, and drug delivery, by controlling the cargo release from artificial cell chassis.

The Role of Lipid Intrinsic Curvature in the Droplet Interface Bilayer.

Model bilayers are constructed from lipids having different intrinsic curvatures using the droplet interface bilayer (DIB) method, and their static physicochemical properties are determined. Geometrical and tensiometric measurements are used to derive the free energy of formation (ΔF) of a two-droplet DIB relative to a pair of isolated aqueous droplets, each decorated with a phospholipid monolayer. The lipid molecules employed have different headgroup sizes but identical hydrophobic tail structure, and each is characterized by an intrinsic curvature value (c0) that increases in absolute value with decreasing size of headgroup. Mixtures of lipids at different ratios were also investigated. The role of curvature stress on the values of ΔF of the respective lipid bilayers in these model membranes is discussed and is illuminated by the observation of a decrement in ΔF that scales as a near linear function of c02. Overall, the results reveal an association that should prove useful in studies of ion channels and other membrane proteins embedded in model droplet bilayer systems that will impact the understanding of protein function in cellular membranes composed of lipids of high and low curvature.

Divalent cations promote huntingtin fibril formation on endoplasmic reticulum derived and model membranes

Huntington's Disease (HD) is caused by an abnormal expansion of the polyglutamine (polyQ) domain within the first exon of the huntingtin protein (htt). This expansion promotes disease-related htt aggregation into amyloid fibrils and the formation of proteinaceous inclusion bodies within neurons. Fibril formation is a complex heterogenous process involving an array of aggregate species such as oligomers, protofibrils, and fibrils. In HD, structural abnormalities of membranes of several organelles develop. In particular, the accumulation of htt fibrils near the endoplasmic reticulum (ER) impinges upon the membrane, resulting in ER damage, altered dynamics, and leakage of Ca2+. Here, the aggregation of htt at a bilayer interface assembled from ER-derived liposomes was investigated, and fibril formation directly on these membranes was enhanced. Based on these observations, simplified model systems were used to investigate mechanisms associated with htt aggregation on ER membranes. As the ER-derived liposome fractions contained residual Ca2+, the role of divalent cations was also investigated. In the absence of lipids, divalent cations had minimal impact on htt structure and aggregation. However, the presence of Ca2+ or Mg2+ played a key role in promoting fibril formation on lipid membranes despite reduced htt insertion into and association with lipid interfaces, suggesting that the ability of divalent cations to promote fibril formation on membranes is mediated by induced changes to the lipid membrane physicochemical properties. With enhanced concentrations of intracellular calcium being a hallmark of HD, the ability of divalent cations to influence htt aggregation at lipid membranes may play a role in aggregation events that lead to organelle abnormalities associated with disease.

Measuring the Transmembrane Registration of Lipid Domains in Droplet Interface Bilayers through Tensiometry.

Diverse collections of lipids self-assemble into domains within biological membranes, and these domains are typically organized in both the transverse and lateral directions of the membrane. The ability of the membrane to link these domains across the membrane's interior grants cells control over features on the external cellular surface. Numerous hypothesized factors drive the cross-membrane (or transverse) coupling of lipid domains. In this work we seek to isolate these transverse lipid-lipid influences in a simple model system using droplet interface bilayers (DIBs) to better understand the associated mechanics. DIBs enable symmetric and asymmetric combinations of domain-forming lipid mixtures within a model bilayer, and the evolving energetics of the membrane may be tracked using drop-shape analysis. We find that symmetric distributions of domain-forming lipids produce long-lasting, gradual shifts in the DIB membrane energetics that are not observed in asymmetric distributions of the lipids where the domain-forming lipids are only within one leaflet. The approach selected for this work provides experimental measurement of the mismatch penalty associated with antiregistered lipid domains as well as measurements of the influence of rafts on DIB behaviors with suggestions for their future use as a model platform.

Droplet Polymer Bilayers for Bioelectronic Membrane Interfacing.

Model membranes interfaced with bioelectronics allow for the exploration of fundamental cell processes and the design of biomimetic sensors. Organic conducting polymers are an attractive surface on which to study the electrical properties of membranes because of their low impedance, high biocompatibility, and hygroscopic nature. However, establishing supported lipid bilayers (SLBs) on conducting polymers has lagged significantly behind other substrate materials, namely, for challenges in membrane electrical sealing and stability. Unlike SLBs that are highly dependent on surface interactions, droplet interface bilayers (DIBs) and droplet hydrogel bilayers (DHBs) leverage the energetically favorable organization of phospholipids at atomically smooth liquid interfaces to build high-integrity membranes. For the first time, we report the formation of droplet polymer bilayers (DPBs) between a lipid-coated aqueous droplet and the high-performing conducting polymer poly(3,4-ethylenedioxythiophene) polystyrenesulfonate (PEDOT:PSS). The resulting bilayers can be produced from a range of lipid compositions and demonstrate strong electrical sealing that outcompetes SLBs. DPBs are subsequently translated to patterned and planar microelectrode arrays to ease barriers to implementation and improve the reliability of membrane formation. This platform enables more reproducible and robust membranes on conducting polymers to further the mission of merging bioelectronics and synthetic, natural, or hybrid bilayer membranes.

Amantadine interactions with phase separated lipid membranes

Amantadine, a small amphilphic organic compound that consists of an adamantane backbone and an amino group, was first recognized as an antiviral in 1963 and received approval for prophylaxis against the type A influenza virus in 1976. Since then, it has also been used to treat Parkinson’s disease-related dyskinesia and is being considered as a treatment for corona viruses. Since amantadine usually targets membrane-bound proteins, its interactions with the membrane are also thought to be important. Biological membranes are now widely understood to be laterally heterogeneous and certain proteins are known to preferentially co-localize within specific lipid domains. Does amantadine, therefore, preferentially localize in certain lipid composition domains? To address this question, we studied amantadine’s interactions with phase separating membranes composed of cholesterol, DSPC (1,2-distearoyl-sn-glycero-3-phosphocholine), POPC (1-palmitoyl-2-oleoyl-glycero-3-phosphocholine), and DOPC (1,2-dioleoyl-sn-glycero-3-phosphocholine), as well as single-phase DPhPC (1,2-diphytanoyl-sn-glycero-3-phos-phocholine) membranes. From Langmuir trough and differential scanning calorimetry (DSC) measurements, we determined, respectively, that amantadine preferentially binds to disordered lipids, such as POPC, and lowers the phase transition temperature of POPC/DSPC/cholesterol mixtures, implying that amantadine increases membrane disorder. Further, using droplet interface bilayers (DIBs), we observed that amantadine disrupts DPhPC membranes, consistent with its disordering properties. Finally, we carried out molecular dynamics (MD) simulations on POPC/DSPC/cholesterol membranes with varying amounts of amantadine. Consistent with experiment, MD simulations showed that amantadine prefers to associate with disordered POPC-rich domains, domain boundaries, and lipid glycerol backbones. Since different proteins co-localize with different lipid domains, our results have possible implications as to which classes of proteins may be better targets for amantadine.

Mechanisms of the Drug Penetration Enhancer Propylene Glycol Interacting with Skin Lipid Membranes.

Very few drugs have the necessary physicochemical properties to cross the skin's main permeability barrier, the stratum corneum (SC), in sufficient amounts. Propylene glycol (PG) is a chemical penetration enhancer that could be included in topical formulations in order to overcome the barrier properties of the skin and facilitate the transport of drugs across it. Experiments have demonstrated that PG increases the mobility and disorder of SC lipids and may extract cholesterol from the SC, but little is known about the molecular mechanisms of drug permeation enhancement by PG. In this work, we have performed molecular dynamics (MD) simulations to investigate the molecular-level effects of PG on the structure and properties of model SC lipid bilayers. The model bilayers were simulated in the presence of PG concentrations over the range of 0-100% w/w PG, using both an all-atom and a united atom force field. PG was found to localize in the hydrophilic headgroup regions at the bilayer interface, to occupy the lipid-water hydrogen-bonding sites, and to slightly increase lipid tail disorder in a concentration-dependent manner. We showed with MD simulation that PG enhances the permeation of small molecules such as water by interacting with the bilayer interface; the results of our study may be used to guide the design of formulations for transdermal drug delivery with enhanced skin permeation, as well as topical formulations and cosmetic products.

Concentration-Dependent Effects of Curcumin on Membrane Permeability and Structure.

Growing evidence suggests that many bioactive molecules can nonspecifically modulate the physicochemical properties of membranes and influence the action of embedded membrane proteins. This study investigates the interactions of curcumin with protein-free model membranes consisting of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and DOPC with cholesterol (4/1 mol ratio). The focus is on the capability of curcumin to modify membrane barrier properties such as water permeability assayed through the droplet interface bilayer (DIB) model membrane. For pure DOPC, our findings show a concentration-dependent biphasic effect: a reduction in water permeability is observed at low concentrations (up to 2 mol %), whereas at high concentrations of curcumin, water permeability increases. In the presence of cholesterol, we observed an overall reduction in water permeability. A combination of complementary experimental methods, including phase transition parameters studied by differential scanning calorimetry (DSC) and structural properties measured by attenuated total reflectance (ATR)-FTIR, provides a deeper understanding of concentration-dependent interactions of curcumin with DOPC bilayers in the absence and presence of cholesterol. Our experimental findings align with a molecular mechanism of curcumin's interaction with model membranes, wherein its effect is contingent on its concentration. At low concentrations, curcumin binds to the lipid-water interface through hydrogen bonding with the phosphate headgroup, thereby obstructing the transport of water molecules. Conversely, at high concentrations, curcumin permeates the acyl chain region, inducing packing disorders and demonstrating evidence of phase separation. Enhanced knowledge of the impact of curcumin on membranes, which, in turn, can affect protein function, is likely to be beneficial for the successful translation of curcumin into effective medicine.

The Signature of Fluctuations of the Hydrogen Bond Network Formed by Water Molecules in the Interfacial Layer of Anionic Lipids

As the water molecules found at the interface of lipid bilayers exhibit distinct structural and reorientation dynamics compared to water molecules found in bulk, the fluctuations in their hydrogen bond (HB) network are expected to be different from those generated by the bulk water molecules. The research presented here aims to gain an insight into temperature-dependent fluctuations of a HB network of water molecules found in an interfacial layer of multilamellar liposomes (MLVs) composed of anionic 1,2-dimyristoyl-sn-glycero-3-phospho-L-serine (DMPS) lipids. Besides suspending DMPS lipids in phosphate buffer saline (PBS) of different pH values (6.0, 7.4, and 8.0), the changes in HB network fluctuations were altered by the incorporation of a non-polar flavonoid molecule myricetin (MCE) within the hydrocarbon chain region. By performing a multivariate analysis on the water combination band observed in temperature-dependent FTIR spectra, the results of which were further mathematically analyzed, the temperature-dependent fluctuations of interfacial water molecules were captured; the latter were the greatest for DMPS in PBS with a pH value of 7.4 and in general were greater for DMPS multibilayers in the absence of MCE. The presence of MCE made DMPS lipids more separated, allowing deeper penetration of water molecules towards the non-polar region and their restricted motion that resulted in decreased fluctuations. The experimentally observed results were supported by MD simulations of DMPS (+MCE) lipid bilayers.

Lipid Microfluidic Biomimetic Models for Drug Screening: A Comprehensive Review

AbstractDeveloping new drugs is a complex, time‐consuming, and expensive process, essential to identify potential pharmacokinetic issues in the early stages to avoid investment in nonpromising candidates. Nearly half of all drug targets and key drug‐metabolizing enzymes are found in intracellular environments, compartmentalized by semipermeable barriers, the cell membranes. Inspired by their lipidic bilayer structure, lipid‐based biomimetic platforms are being developed to understand the biochemical and biophysical processes at the cellular membrane level. Considering the pharmaceutical industry's demands for efficient in vitro high throughput screening tools, microfluidic technology emerges as a promising solution to address challenges in lipid biomimetic models for screening applications. This involves the transformation of commonly used lipid‐based biomimetic models, like supported lipid bilayers and lipid vesicles, to miniaturized approachs and their evolution into a new generation of bilayer models. These include pore‐suspended and free‐standing lipid bilayers, black lipid membranes, and droplet interface bilayers. This review provides an overview of both generations of lipid biomimetic models used in drug‐membrane screening applications. Moreover, it delves into the intricacies of their production through microfluidic approaches and examines their screening applications in drug‐membrane interaction. The review concludes with a critical analysis of potential future directions in this rapidly evolving field.

Role of the midplane interface of asymmetric bilayers

Role of the midplane interface of asymmetric bilayers

Hidden phonon highways promote photoinduced interlayer energy transfer in twisted transition metal dichalcogenide heterostructures.

Vertically stacked van der Waals (vdW) heterostructures exhibit unique electronic, optical, and thermal properties that can be manipulated by twist-angle engineering. However, the weak phononic coupling at a bilayer interface imposes a fundamental thermal bottleneck for future two-dimensional devices. Using ultrafast electron diffraction, we directly investigated photoinduced nonequilibrium phonon dynamics in MoS2/WS2 at 4° twist angle and WSe2/MoSe2 heterobilayers with twist angles of 7°, 16°, and 25°. We identified an interlayer heat transfer channel with a characteristic timescale of ~20 picoseconds, about one order of magnitude faster than molecular dynamics simulations assuming initial intralayer thermalization. Atomistic calculations involving phonon-phonon scattering suggest that this process originates from the nonthermal phonon population following the initial interlayer charge transfer and scattering. Our findings present an avenue for thermal management in vdW heterostructures by tailoring nonequilibrium phonon populations.

Influence of lipid vesicle properties on the function of conjugation dependent membrane active peptides.

Membrane active peptides (MAPs) can provide novel means to trigger the release of liposome encapsulated drugs to improve the efficacy of liposomal drug delivery systems. Design of MAP-based release strategies requires possibilities to carefully tailor the interactions between the peptides and the lipid bilayer. Here we explore the influence of lipid vesicle properties on the function of conjugation-dependent MAPs, specifically focusing on two de novo designed peptides, JR2KC and CKV4. Utilizing liposomes with differences in size, lipid composition, and surface charge, we investigated the mechanisms and abilities of the peptides to induce controlled release of encapsulated cargo. Our findings indicate that liposome size modestly affects the structural changes and function of the peptides, with larger vesicles facilitating a minor increase in drug release efficiency due to higher peptide-to-liposome ratios. Notably, the introduction of negatively charged lipids significantly enhanced the release efficiency, predominantly through electrostatic interactions that favor peptide accumulation at the lipid bilayer interface and subsequent membrane disruption. The incorporation of cholesterol and a mix of saturated and unsaturated lipids was shown to alter the vesicle's phase behavior, thus modulating the membrane activity of the peptides. This was particularly evident in the cholesterol-enriched liposomes, where JR2KC induced lipid phase separation, markedly enhancing cargo release. Our results underscore the critical role of lipid vesicle composition in the design of MAP-based drug delivery systems, suggesting that precise tuning of lipid characteristics can significantly influence their performance.