Mixed Monolayers Research Articles

Investigating Molecular Junctions Based on Mixed Self-Assembled Monolayers to Understand the Impact of Intermolecular Interactions on Transport.

To interrogate the importance of intermolecular interactions on charge transport at the nanoscale, we investigate molecular tunnel junctions based on mixed self-assembled monolayers (SAMs) of 1-alkyl (CnT) thiols and their fluorinated counterparts (F-CnT) that have substantially different tunneling conductances. Experiments on mixed CnT1-x:F-CnTx SAMs between Au contacts reveal a strongly nonlinear (exponential) dependence of the tunneling conductance G on composition x, a behavior that is tempting to assign to the strong impact of intra-SAM intermolecular interactions. However, analysis suggests that the exponential dependence of G on x does not arise from intra-SAM intermolecular interactions, but instead emerges from the work function modification of the Au electrode which varies linearly with x.

Extracting the Heterogeneous 3D Structure of Molecular Films Using Higher Dimensional SFG Microscopy.

Ultrathin molecular films are widespread in both natural and industrial settings, where details of the molecular structure such as density, out-of-plane tilt angles, and in-plane directionality determine their physicochemical properties. Many of these films possess important molecular-to-macroscopic heterogeneity in these structural parameters, which have traditionally been difficult to characterize. Here, we show how extending sum-frequency generation (SFG) microscopy measurements to higher dimensionality by azimuthal-scanning can extract the spatial variation in the three-dimensional molecular structure at an interface. We extend the commonly applied theoretical assumptions used to analyze SFG signals to the study of systems possessing in-plane anisotropy. This theoretical framework is then applied to a phase-separated mixed lipid monolayer to investigate the variation in molecular density and 3D orientation across the chirally packed lipid domains. The results show little variation in out-of-plane structure but a distinct micron-scale region at the domain boundaries with a reduction in both density and in-plane ordering.

Probing Deuteration-Induced Phase Separation in Supported Lipid Monolayers using Hyperspectral TERS Imaging.

In this study, we investigate the impact of deuteration on the formation of phase-separated domains in supported lipid monolayers using hyperspectral Tip-Enhanced Raman Spectroscopy (TERS) imaging. The intricate organization of biological membranes plays a crucial role in cellular functions. Various factors that influence domain formation have been identified in previous studies such as lipid tail length and cholesterol concentration. Deuterium labeling of lipids has proven useful for probing cellular structures and dynamics, but its impact on lipid phase separation remains underexplored. By examining 1:1 mixed monolayers of dipalmitoylphosphatidylcholine (DPPC) and deuterated DPPC on Au(111) surfaces, we reveal partial segregation of domains rich in deuterated and nondeuterated lipids. This study addresses a gap in knowledge by examining the impact of deuteration on lipid tail behavior, offering new insights into how even subtle structural modifications can influence phase behavior. Furthermore, it demonstrates that TERS can be a powerful, nondestructive, and label-free nanoanalytical tool for analyzing lipid membranes and advance the field of membrane biophysics.

Morphological control of bicontinuous phase-separated patterns by preparing mixed monolayers using non-amphiphilic s-triazine derivatives with three fluorinated chains

In this study, the morphogenesis of the bicontinuous phase separation in mixed monolayers of a non-amphiphilic fluorocarbon derivative without a hydrophilic group and long-chain fatty acids is discussed. These fluorocarbon derivatives contain an s-triazine ring and three fluorocarbon chains. The corresponding fluorocarbon derivatives exhibit high crystallinity in the monolayers, allowing them to maintain crystalline regularity even in the "sea" region of the mixed monolayer that exhibits phase separation. In controlling the bicontinuous pattern, the formation of complex phase-separated morphology in the mixed system of fluorine-based derivatives and comb polymers, along with the high concentration and low diffusion conditions in the mixed hydrocarbon/fluorocarbon system, were examined. It was observed that the condensed phase domains became angular shape at a low temperature (5 °C), and the surface approached a bicontinuous feature at a high temperature (40 °C). With the formation of hydrogenated condensed domains, the "sea" region of fluorocarbon chains lost its order. At this point, the shape of the nanodomains tended to become more circular.

Novel mixed self-assembled monolayers of L-cysteine and methanol on gold surfaces under ambient conditions.

In this work, we carried out an experimental and theoretical study on the formation of self-assembled monolayers of L-cysteine molecules on gold surfaces in the presence of methanol as a solvent. We report for the first time L-cysteine and methanol ordered structures forming a mixed self-assembled mono-layer on Au(100) surfaces under ambient conditions. Finger-like ordered structures with a relative height of 0.10-0.20 nm, average width of 2.0 nm and variable lengths were observed using scanning tunneling microscopy under room temperature and ambient pressure conditions. Using X-ray photoemission spectroscopy, it was determined that L-cysteine molecules bind to the gold surface through the sulfur atom of their thiol group in two molecular configurations: neutral and zwitterionic. We found that the finger-like structures are the result of complex interactions of L-cysteine molecules with gold surfaces and L-cysteine molecules with methanol molecules and among all three components of the system (L-cysteine + methanol + gold surfaces). These interactions were detected through attenuated total reflectance-Fourier transform infrared spectroscopy. Furthermore, adsorbate/substrate interactions were studied by employing ab initio calculations using density functional theory, resulting in molecular arrangements formed by chains of L-cysteine pairs surrounded by physisorbed methanol molecules.

Interactions of Alkali Ions and Phospholipid Monolayers at Organic-Water Interfaces

The self-assembled phospholipids monolayers at interfaces between two immiscible electrolyte solutions (ITIES) are commonly used to study the interactions between cell membranes and species passing in and out through membrains such as ions, drugs, and other nutrients. In this study, we utilized electrochemical techniques such as open circuit potential (OCP), cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS) to study the pure phospholipd monolayer formed by 1,2-Dioleoyl-sn-glycero-3-phosphocholine (DOPC) and its mixture with 1,2-dioleoyl-sn-glycero-3-phospho-(1'-racglycerol) (sodium salt) (DOPG) at 1,2-dichloroethane-water interfaces. Our study has shown that at higher applied electric potentials, there seems to be no change in the facilitation of cation transfers by DOPC/DOPG monolayer compared to DOPC monolayer. However, at lower applied potentials, the DOPGs in the mixed monolayer seemed to leave the interface under the influence of the applied electric field, indicated by both the higher capacitance obtained throught the EIS measurements and the higher currents from the CV measurements compared to results obtained from the sample consisted of the pure DOPC monolayer. Furthermore, our study also showed a general rise in capacitance when incorporating heavier alkali ions in the aqueous phase for the sample with the mixture of DOPC/DOPG at higher applied electric potentials.

Role of Density and Conformational Composition in the Surface-to-Bulk Molecular Dosing of Photosensitive Surfactant Monolayers.

Poorly water-soluble photosensitive monolayers might enable very precise control of the rate and number of desorbing molecules by controlling both the monolayer density and conformational composition. In this perspective, we systematically characterized the interfacial behavior of Langmuir monolayers consisting of a poorly water-soluble azobenzene-containing surfactant as a function of its trans/cis ratio. Precise control of the conformational ratio was achieved by controlling the UV irradiation time, allowing researchers to investigate compositions spanning from 100% trans to 90% cis. Our results demonstrate that in 100% trans monolayers, molecules do not desorb with compression until a threshold area is reached. Instead, the number of molecules desorbing in mixed trans-cis monolayers can be modulated by controlling both the composition and the compression rate. Additionally, the desorption rate at constant density is also strongly composition-dependent, and it accounts for two different regimes with two different characteristic times. We will show that trans molecules mostly desorb according to the slow regime while cis molecules conform to the fast one, but the two conformers mutually influence each other.

Impact of cholesterol on the structure and phase separation of DPPC Langmuir monolayers: Experiments and simulations

Cholesterol is a lipid that plays a key role mainly in the plasma membrane of animal cells, determining their structural and mechanical properties. While Langmuir monolayers have been a traditional model for studying these membranes, they may not fully capture microscopic phenomena. We studied mixed Langmuir monolayers of DPPC and cholesterol in various proportions, using a Langmuir trough for surface compression isotherms and micro-Brewster Angle Microscopy (MicroBAM) for imaging. Furthermore, atomistic Molecular Dynamics (MD) simulations were used to examine molecular distributions, geometric conformations, and emergence of a gas phase in the monolayers. Both experimental and simulation results were compared to obtain a comprehensive understanding. The results reveal strong attraction between DPPC tails and cholesterol, increasing monolayer stiffness and density. These interactions align the lipid tails more perpendicularly to the water surface, effectively minimizing their projected area and preventing tail entanglement. Consequently, the reduced flexibility triggers a phase separation in the monolayer at smaller areas per lipid, with low-density voids and denser regions, as observed in both MicroBAM and simulations. These outcomes emphasize the critical role of cholesterol in biological membranes. Finally, the consistency of MD simulations with experiments validate them as a valuable tool for investigating lipid monolayer behavior.

Adhesion promotion and corrosion resistance of mixed phosphonic acid monolayers on AA 2024

Mixed monolayers were used to prepare surfaces of AA 2024 with precisely controlled corrosion protective and adhesive properties. In this study, the corrosion inhibition and adhesion promotion as a function of the composition of mixed phosphonic acid monolayers on AA 2024 was investigated. Mixed monolayers were formed by competitive adsorption of n-dodecylphosphonic acid (DPA) and 12-aminododecylphosphonic acid (ADPA) from ethanolic solution. Their compositions were determined by X-ray photoelectron spectroscopy. Atomic force microscopy studies and polarization modulation infrared reflection–absorption spectroscopy as well as contact angle studies proved the formation of monolayers with varying surface chemistry. The wet-adhesion strength was tested by 90° peel tests after application of an epoxy-amine adhesive. Linear sweep voltammetry was performed to evaluate the corrosion inhibition of the monolayers, and the corrosion resistance of the metal/adhesive composite was investigated by means of its corrosive delamination behavior. The electrochemical measurements demonstrated that reducing the surface concentration of ADPA improved the corrosion inhibition of the monolayer. However, the corrosive delamination experiments revealed that the improved corrosion inhibition by the self-organized DPA is of minor importance for the corrosion behavior of the metal/adhesive composite, as the adhesive properties dominate.

Surface plasmon resonance biosensor with anti-crossing modulation readout

A novel approach to surface plasmon resonance (SPR) biosensors providing simplified label-free monitoring of biomolecular affinity binding events is reported. It is based on the interrogation of anti-crossing surface plasmon modes traveling along opposite interfaces of a thin metal film on the top of a tailored multi-periodic grating structure. It allows for diffraction-based backside excitation of surface plasmons without the need of optical matching of the sensor chip to a prism and it allows avoiding of optical probing through the analyzed liquid sample. In conjunction with low angular dispersion of resonantly excited surface plasmon modes, it provides sensitive and versatile optical interrogation of SPR changes associated with biomolecular binding-induced refractive index variations. Direct readout with a fiber optic probe, as well as multi-channel configuration compatible with regular SPR readers, is implemented with the use of sensor chips prepared by mass production-compatible UV-nanoimprint lithography. The potential of the reported SPR sensor chips is illustrated by its ability to characterize affinity interaction of antibodies specific to cancer biomarker CSPG4 on antifouling mixed thiolated self-assembled monolayer with zwitterionic carboxybetaine and sulfobetaine headgroups.

Formation of two-dimensional mixed monolayers of integrated-cellulose nanofibers and starch nanoparticles using cellulose acetate and soluble starch

In this study, mixed monolayers comprising starch and cellulose nanofibers are prepared on the water surface and effectively controlled their surface morphologies. Through the spreading of cellulose acetate on the water surface, we achieve the preparation of integrated films with the spontaneous formation of nanocellulose. It is confirmed that starch, which is insoluble in the spreading solvent, is solubilized through a soluble treatment and spreads into a monolayer on the water surface. Upon mixing the nanocellulose integrated layer and starch particle layer, the morphology changes based on the mixed ratio of these components. In the monolayer film of a 1:1 mixture of cellulose acetate and soluble starch, the morphology predominantly consists of fibers, with particulate aggregates incorporated here and there. Furthermore, when the ratio changes to 1:5, the mixed monolayer transforms into a single particle layer, while the mixed monolayer evolves into a fibrous integrated film at a ratio of 5:1. Meanwhile, from the evaluation of the surface pressure-area isotherms, it is predicted that both components constitute an ideal mesoscopic miscible system. In addition, in the subphase temperature dependence of the cellulose acetate:soluble starch = 1:1 mixed monolayer, fibers are promoted under low-temperature conditions, and substantial domains are formed under high-temperature conditions. Notably, the mixed film remains amorphous at all ratios and exhibits low surface free energy, simultaneously suggesting hydrophobic and oil-repellent properties.

Effect of high sodium ion level on the interaction of AmB with a cholesterol-rich phospholipid monolayer.

Invasive fungal infections are a primary reason for high mortality in immunocompromised people, especially in critically ill patients, such as intensive care unit (ICU) patients, advanced cancer patients, or severe burn patients. Hypernatremia also can increase mortality in severely ill patients. Amphotericin B (AmB) is the gold standard for treating infections, but in severely ill patients, AmB can cause hematotoxicity when administered intravenously due to its interaction with cholesterol on red blood cell membranes. This results in limited doses of AmB and affects the treatment of infections. The proportion of cholesterol molecules in membrane lipids in red blood cells is as high as 50mol%, and the sodium ions can influence the interaction between AmB and lipids on the membrane. Therefore, in the complex clinical situation of a severely ill patient with a fungal infection and hypernatremia, the interaction between amphotericin B and the red blood cell membranes is worth studying in depth. In this work, the interaction between AmB and the dipalmitoyl phosphatidylcholine (DPPC)/cholesterol mixed monolayer in the presence of high sodium ion levels was studied when the proportion of cholesterol was 50%. The results show that the effect of AmB on reducing the monolayer's area at a high level of sodium ions is slightly stronger at 30mN/m. The effect of AmB on reducing the elastic modulus of the DPPC/Chol monolayer is significantly weakened by a high sodium ion level, compared with the level of sodium ions at normal physiological concentration. The higher the sodium ion concentration, the weaker the intermolecular force of the DPPC/Chol/AmB mixed monolayers. The scanning electron microscope (SEM) and atomic force microscopy (AFM) observations suggest that at a high sodium ion level, the presence of AmB significantly reduces the surface roughness of the DPPC/Chol monolayer. AmB may bind to cholesterol molecules, and it isolates cholesterol from the monolayer, resulting in a reduced height of the cholesterol-rich monolayer and an increasingly dispersed monolayer region. The results are beneficial to understanding the mechanism of impact of a high sodium ion level on the relationship between AmB and red blood cell membranes rich in cholesterol and are valuable for understanding the hemolytic toxicity of AmB to red blood cells at a high sodium ion level.

Antioxidant activity of bottlebrush copolymers and its self-assembly in mixed monolayers with cholesterol in the presence of cerium nitrate

Antioxidant activity of bottlebrush copolymers and its self-assembly in mixed monolayers with cholesterol in the presence of cerium nitrate

Electrografted mixed organic monolayers as antibacterial coatings for implantable biomedical devices

Bacterial infections associated with the implantation of biomedical devices belong to one of the leading causes of their failure. Accordingly, novel methods of surface modifications are highly required to prevent bacterial adhesion and limit the use of antibiotics. Electrochemical grafting of organic moieties is a well-known method of surface modification at the nanoscale level, allowing for the modulation of surface wettability, roughness, and the ability to enhance/reduce cellular adhesion, among others. In this work, the presence of an organic coating formed through the electrografting of a mixture of diazonium salts is proposed to tailor interactions between the surface and a living matter. Through the application of diazonium compounds possessing different functional groups, it is possible to alter electrochemical and surface properties, as well as cell survivability and anti-adhesive activity towards bacteria. It is shown that the presence of organic layers results in 4.5-fold increase in the wettability of the surface and 1.5-fold increase in roughness, leading to the 84% decrease in bacterial adhesion without affecting surface's biocompatibility. In this way, mixed organic monolayers formed through the electroreduction of a mixture of diazonium salts can serve as antibacterial coatings suitable for implantable biomedical devices.

Creation of Organic/Inorganic Hybrids in Two‐Dimensional Organized Films Using Natural Materials and Control of Their Morphology

AbstractStarch, an insoluble natural polymer, can be spread into a Langmuir monolayer on the surface of water as amylodextrin by solubilization, where it forms a spherical single‐particle layer at the air–water interface. In this study, we fabricated a two‐dimensional mixed monolayer from soluble starch and organo‐modified montmorillonite and attempted to control its morphology by varying the mixing ratio. The behavior of the organo‐modified montmorillonite was dependent on the spreading solvent and miniaturization was possible using a suitable solvent for spreading insoluble starch. Although both materials formed phase‐separated systems, nearly homogeneous particle layers were formed in some cases because of clay miniaturization. However, X‐ray photoelectron spectroscopy showed that the clay components remained intact and a rectangular morphology derived from aluminosilicate was observed in the mixed film with a high clay ratio. Functionalization as a mixed film clearly demonstrated the hydrophilic properties imparted by the starch particles and the selective adsorption of biomolecules on the clay surface.

Surface miscibility of Gemini surfactants and DOPE in binary mixed monolayers

AbstractSurface pressure (π)–molecular area (A) isotherms were gathered to characterize the packing of binary mixed Langmuir monolayers of 1,2‐dioleoyl‐sn‐glycero‐3‐phosphoethanolamine (DOPE) and one of two Gemini surfactants (GS), N,N‐bis(dimethyloctadecyl)‐1,7‐nonanediammonium dibromide (18‐7‐18) or 1,9‐bis(octadecyl)‐1,1,9,9‐tetramethyl‐5‐amino‐1,9‐nonanediammonium dibromide (18‐7NH‐18) of varying molar fractions. Information about miscibility behavior was derived from the π–A curves by examining the excess free energy of mixing (ΔGexc) that was calculated through the surface area additivity rule. Surface compressibility modulus (Cs−1) was also used to characterize intermolecular interactions. Mutual interactions between GS and DOPE were analyzed in terms of excess Gibbs energy of mixing and the value of this parameter depended strongly on the composition of the mixed film. GS and DOPE are generally miscible as DOPE reduces intermolecular repulsion between highly charged GS molecules leading to the formation of more densely packed mixed monolayers. However, GS and DOPE are immiscible in equimolar mixtures due to tail group packing mismatch between saturated and unsaturated alkyl chains. The prevalence of attractive synergistic interactions in the monolayers studied differs from a previous finding of antagonistic mixing behavior in GS/DOPE micelles. These results contribute to the understanding of GS‐lipid interactions and packing that are critical to the in vitro and in vivo stability of liposomes composed of these molecules used for non‐viral gene therapy applications.

Spiral packing and chiral selectivity in model membranes probed by phase-resolved sum-frequency generation microscopy

Since the lipid raft model was developed at the end of the last century, it became clear that the specific molecular arrangements of phospholipid assemblies within a membrane have profound implications in a vast range of physiological functions. Studies of such condensed lipid islands in model systems using fluorescence and Brewster angle microscopies have shown a wide range of sizes and morphologies, with suggestions of substantial in-plane molecular anisotropy and mesoscopic structural chirality. Whilst these variations can significantly alter many membrane properties including its fluidity, permeability and molecular recognition, the details of the in-plane molecular orientations underlying these traits remain largely unknown. Here, we use phase-resolved sum-frequency generation microscopy on model membranes of mixed chirality phospholipid monolayers to fully determine the three-dimensional molecular structure of the constituent micron-scale condensed domains. We find that the domains possess curved molecular directionality with spiralling mesoscopic packing, where both the molecular and spiral turning directions depend on the lipid chirality, but form structures clearly deviating from mirror symmetry for different enantiomeric mixtures. This demonstrates strong enantioselectivity in the domain growth process and indicates fundamental thermodynamic differences between homo- and heterochiral membranes, which may be relevant in the evolution of homochirality in all living organisms.

Nanoscale Structure of Lipid-Gemini Surfactant Mixed Monolayers Resolved with AFM and KPFM Microscopy.

Drug delivery vehicles composed of lipids and gemini surfactants (GS) are promising in gene therapy. Tuning the composition and properties of the delivery vehicle is important for the efficient load and delivery of DNA fragments (genes). In this paper, we studied novel gene delivery systems composed of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), 1,2-dipalmitoyl-sn-3-phosphocholine (DPPC), and GS of the type N,N-bis(dimethylalkyl)-α,ω-alkanediammonium dibromide at different ratios. The nanoscale properties of the mixed DOPC-DPPC-GS monolayers on the surface of the gene delivery system were studied using atomic force microscopy (AFM) and Kelvin probe force microscopy (KPFM). We demonstrate that lipid-GS mixed monolayers result in the formation of nanoscale domains that vary in size, height, and electrical surface potential. We show that the presence of GS can impart significant changes to the domain topography and electrical surface potential compared to monolayers composed of lipids alone.

Ultrasensitive, label-free, electrochemical detection of miRNA-206 in human plasma: A potential biomarker associated with Alzheimer’s disease

An impedance-based biosensor for the ultrasensitive, selective, and label-free detection of a blood miRNA associated to Alzheimer disease (AD), miRNA-206, was developed. The principle was grounded in the changes in the charge transfer resistance (RCT) as an effect of intramolecular forces between miRNAs and ferro/ferricyanide in a well-structured transducer platform. A compact well-ordered mixed monolayer made of co-immobilized miRNA capture to 6-mercapto-1-hexanol (MCH) in a 1:4 M ratio (at 37 °C), uplifted the performance of the sensor through effectively assisting the orientation of the oligonucleotides. In this work, the remarkable response of the sensor was generated through new insights into the use of different moieties of miRNA capture to MCH, aiming to control interfacial constants, surface densities, and hybridization efficiency.A very low limit of detection, 0.15 aM, is achieved and the sensor has a wide linear dynamic range (from 1 aM to 1 μM), high selectivity to mismatches, low non-specific binding of proteins (BSA) and good stability (<10 % change in response after 14 days storage). Importantly, the sensor successfully measured miRNA-206 concentrations in real plasma samples (>95 % recovery), correlating directly with qPCR results. Nanomolar concentrations of miRNA-206 were found in the plasma of confirmed AD patients, while healthy controls, had a concentration of pM or lower. The biosensor's ability to quantitatively detect miRNA-206 in plasma without target amplification, e.g., using PCR, is significant, opening the possibility of developing a point-of-care diagnostic device for AD screening, contributing to clinical trials and patient care.

Mixed Self-Assembled Monolayers for High-Photovoltage Tin Perovskite Solar Cells

Mixed Self-Assembled Monolayers for High-Photovoltage Tin Perovskite Solar Cells