Headgroup Hydration Research Articles

Spontaneous nanosized liposome formation from crude dried lecithin upon addition of glycerol

Nanosized liposomal vesicles (NLV) were successfully prepared using natural sunflower lecithin without the use of high-pressure homogenization or filtration. Upon glycerol addition to dispersions of lecithin multilamellar vesicles (MLVs), these broke down spontaneously to liposomes with diameters in the range of 100–200 nm. Static light scattering demonstrated that glycerol addition above 30% (w/w) induced the complete transformation of MLVs into NLVs. Langmuir trough compression experiments showed a two-region compressional behavior. Upon 62% (w/w) glycerol addition, the compressional modulus of the liposomes decreased from 18.5 to 8.13 mN/m. Water activity and pulse NMR measurements also showed a divergence in behavior above 30% (w/w) glycerol. Liposomes were not birefringent in water but became strongly birefringent at and above 30% (w/w) glycerol, as determined by polarized light microscopy, and lost all birefringence above 80% (w/w). This was interpreted as the induction of stress-birefringence in the phospholipid bilayers above 30% (w/w) glycerol, and a relaxation of such stress above 80% (w/w) glycerol. We hypothesize that the mixture of phospholipids in the lecithin results in an effective non-zero intrinsic curvature for the molecular mixture, which lowers the bending energy of the bilayer, allowing for an easier break-up upon mixing. Secondly, glycerol addition decreases attractive van der Waals’ interaction between lamellae in an MLV, thus weakening the multilamellar liposome walls. Glycerol also affects bilayer stability by strengthening the hydrogen bond network of water, which will affect phospholipid headgroup hydration. All these factors result in the spontaneous breakdown of MLVs into NLVs.

Role of zwitterionic lipid headgroups on monolayer formation and interfacial dilatational rheology in binary mixtures of phospholipids and cholesterol: A pendant drop tensiometer study

The complex composition of biological membranes, comprising a diverse array of lipids with unique moieties, has garnered increased attention due to the recognized roles of lipids in membrane stability and biological processes. Even subtle changes in phospholipid headgroups and fatty acyl tails profoundly affect the formation and interfacial dynamics of lipid monolayers at the air-water interface. However, the molecular-level understanding of their intermolecular forces and interactions during these processes, directly relating to the lipid chemical structures, is not well-explored. To better understand these complex physicochemical phenomena, simplified model monolayers with precise control over lipid types and compositions are utilized. In this study, we employ the pendant drop tensiometer technique to investigate the formation and interfacial rheology of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE) monolayers, with varying amounts of cholesterol (CHOL) for the first time. These two phospholipids, with identical C16:0 acyl tails but different headgroups, exhibit marked differences in their interfacial interactions with CHOL and water molecules, consequently affecting monolayer formation and rheology. In the absence of CHOL, DPPE monolayers typically display a lower dilatational modulus than DPPC, attributed to increased headgroup hydration. However, introducing CHOL reverses this trend, resulting in stiffer DPPE-CHOL monolayers compared to DPPC-CHOL. With CHOL, we observe its well-known condensation effect on DPPC monolayers, yet for DPPE monolayers, both condensation and expansion effects are noted, contingent on CHOL amount. We anticipate this work will not only deepen our fundamental understanding of the structure-composition-property relationships in lipid molecules but also provide a robust foundation for comprehending more intricate biological systems.

Experimental Investigations and MD Simulation on Nanoparticle-Enhanced CO2-Responsive Foam (NECRF): Implications on CO2-EOR.

CO2-responsive foam (CRF) is a highly promising candidate for CO2-enhanced oil recovery (CO2-EOR) because it displays higher stability than the surfactant-stabilized foam owing to the formation of robust wormlike micelles (WLMs) upon exposure to CO2. In this work, the nanoparticle-enhanced CO2-responsive foam (NECRF) was properly prepared using lauryl ether sulfate sodium (LES)/diethylenetriamine/nano-SiO2, and its interfacial properties and EOR potential were experimentally and numerically assessed, aiming to explore the feasibility and effectiveness of NECRF as a novel CO2-EOR technique. It was found that the interfacial expansion elastic modulus increased 6-fold after CO2 stimulation. The modulus continued to increase with the introduction of nano-SiO2 owing to the pronounced synergistic effect of WLMs and nanoparticles. In addition to increasing the viscosity of the foaming liquid, WLMs and nano-SiO2 enhanced the shearing resistance of the NECRF as well. Calculations demonstrated that both the coarsening rate and the size distribution uniformity coefficient of NECRF were markedly lower than that of the LES foam, which subsequently inhibited NECRF decay and greatly improved its dynamic stability. Besides, molecular dynamics simulation revealed that adding inorganic salts to NECRF could notably enhance the foaming performance due to the intensified hydration of surfactant head groups and reduced binding energy of neighboring molecules. Nuclear magnetic resonance-assisted core flooding experiments validated the exceptional capacity of NECRF to sweep the low-permeability region and improve the conformance profile. Overall, these findings may provide valuable insights into the development and application of novel materials and strategies for the CO2-EOR.

Antimicrobial Peptide Coating of TiO2 Nanoparticles for Boosted Antimicrobial Effects

AbstractThis study explores the coating of photocatalytic nanoparticles with antimicrobial peptides (AMPs) for boosted antimicrobial effects, and how such effects depend on AMP properties. For this, TiO2 nanoparticles are coated with the AMP KYE21 or its hydrophobically enhanced variant WWWKYE21. Mirroring effects of free peptides, coated nanoparticles displayed higher binding and UV‐induced degradation for bacteria‐like than for mammalian‐like membranes. In addition, they degraded bacterial lipopolysaccharides (LPS). WWWKYE21‐coated nanoparticles displayed higher binding to LPS and bacteria‐like membranes and photocatalytic degradation, although saturation effects are found at high nanoparticle binding. Neutron reflectometry showed that binding of peptide‐coated nanoparticles to bacteria‐like membranes resulted in partial lipid removal in the absence of UV, but that UV illumination caused additional degradation, featuring increases in the hydration of headgroup and acyl chain regions. For LPS, UV induced removal of its outer O‐antigen region. Analogous to findings in model systems, antimicrobial effects of peptide‐coated nanoparticles against Escherichia coli bacteria on illumination are pronounced, while toxicity against human monocytes remained low. Altogether, results show that AMP coating boosts the antimicrobial effects of photocatalytic nanoparticles without causing cell toxicity. From a broader perspective, the study points to the potential of nanoarchitectonic combination of component properties for the design of composite NP properties.

Surfactant-Mediated Structural Modulations to Planar, Amphiphilic Multilamellar Stacks.

The hydrophobic effect, a ubiquitous process in biology, is a primary thermodynamic driver of amphiphilic self-assembly. It leads to the formation of unique morphologies including two highly important classes of lamellar and micellar mesophases. The interactions between these two types of structures and their involved components have garnered significant interest because of their importance in key biochemical technologies related to the isolation, purification, and reconstitution of membrane proteins. This work investigates the structural organization of mixtures of the lamellar-forming phospholipid 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and two zwitterionic micelle-forming surfactants, being n-dodecyl-N,N-dimethyl-3-ammonio-1-propanesulfonate (Zwittergent 3-12 or DDAPS) and 1-oleoyl-2-hydroxy-sn-glycero-3-phosphocholine (O-Lyso-PC), when assembled by water vapor hydration with X-ray diffraction measurements, brightfield optical microscopy, wide-field fluorescence microscopy, and atomic force microscopy. The results reveal that multilamellar mesophases of these mixtures can be assembled across a wide range of POPC to surfactant (POPC:surfactant) concentration ratios, including ratios far surpassing the classical detergent-saturation limit of POPC bilayers without significant morphological disruptions to the lamellar motif. The mixed mesophases generally decreased in lamellar spacing (D) and headgroup-to-headgroup distance (Dhh) with a higher concentration of the doped surfactant, but trends in water layer thickness (Dw) between each bilayer in the stack are highly variable. Further structural characteristics including mesophase topography, bilayer thickness, and lamellar rupture force were revealed by atomic force microscopy (AFM), exhibiting homogeneous multilamellar stacks with no significant physical differences with changes in the surfactant concentration within the mesophases. Taken together, the outcomes present the assembly of unanticipated and highly unique mixed mesophases with varied structural trends from the involved surfactant and lipidic components. Modulations in their structural properties can be attributed to the surfactant's chemical specificity in relation to POPC, such as the headgroup hydration and the hydrophobic chain tail mismatch. Taken together, our results illustrate how specific chemical complexities of surfactant-lipid interactions can alter the morphologies of mixed mesophases and thereby alter the kinetic pathways by which surfactants dissolve lipid mesophases in bulk aqueous solutions.

Assessment of DPPC Liposome Disruption by Embedded Tocopheryl Malonate

In this study, the effect of α-tocopheryl malonate (TM) on physical and structural properties of DPPC liposomes was investigated using ANS fluorescence, DPH, and TMA–DPH anisotropy fluorescence and differential scanning calorimetry (DSC) methods. The presence of embedded TM in DPPC liposomes caused alteration in its phase transition temperatures, structural order, dynamics, and hydration of head groups increasingly with growing TM concentration. The ANS fluorescence results demonstrated that increasing TM presence in the DPPC gel phase due to interrupted membrane structure caused the formation of new binding sites. Temperature investigations in the range of 20 °C to 60 °C showed that increasing temperature rises ANS fluorescence which reaches local and global maxima at 36 °C and 42 °C, respectively. The rising TM concentration at the phase transition temperature of DPPC led to the lowering of ANS fluorescence, indicating a decreased binding of ANS. Simultaneously, during heating, a roughly 10-nm shift of ANS emission maximum was observed. The results indicated that in the fluid phase, the observed quenching appears as a result of increasing accessibility of water molecules into ANS in this region. The DPH results indicated that in the gel phase presence of TM introduced disorder in the hydrophobic acyl chain region led to its fluidization. The TMA–DPH results indicated an increasing disorder in the interface region and an increasing hydration of head group atoms at the surface of the membrane. The increasing concentration of TM results in the formation of multicomponent DSC traces, suggesting the formation of another structural phase. The applied methods proved that the incorporation of TM into DPPC membrane results in the interaction of malonate moiety with DPPC head group atoms in the interphase layer and induces the interruption in the membrane packing order, leading to its structural changes. The presented results show that TM presence could regulate the membrane properties, thus it may indicate one of the possible mechanisms responsible for the effective disruption of cell membranes by TM. The knowledge of molecular mechanism how TM interacts with the membrane will help to elucidate its possible pharmacological activity.

Incorporation of acridine orange and methylene blue in Langmuir monolayers mimicking releasing nanostructures

The efficiency of methylene blue (MB) and acridine orange (AO) for photodynamic therapy (PDT) is increased if encapsulated in liposomes. In this paper we determine the molecular-level interactions between MB or AO and mixed monolayers of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-dipalmitoyl-sn-glycero-3-phospho-(1′-rac-glycerol) (DPPG) and cholesterol (CHOL) using surface pressure isotherms and polarization-modulated infrared reflection absorption spectroscopy (PM-IRRAS). To increase liposome stability, the effects from adding the surfactants Span® 80 and sodium cholate were also studied. Both MB and AO induce an expansion in the mixed monolayer, but this expansion is less significant in the presence of either Span® 80 or sodium cholate. The action of AO and MB occurred via coupling with phosphate groups of DPPC or DPPG. However, the levels of chain ordering and hydration of carbonyl and phosphate in headgroups depended on the photosensitizer and on the presence of Span® 80 or sodium cholate. From the PM-IRRAS spectra, we inferred that incorporation of MB and AO increased hydration of the monolayer headgroup, except for the case of the monolayer containing sodium cholate. This variability in behaviour offers an opportunity to tune the incorporation of AO and MB into liposomes which could be exploited in the release necessary for PDT.

Synergistic effects of Gemini cationic surfactants with multiple quaternary ammonium groups and anionic surfactants with long EO chains in the mixed systems

In this study, two different anionic surfactants containing long polyoxyethylene chains involving sodium fatty alcohol ether carboxylates (AE9C) as well as isomeric sodium fatty alcohol ether sulfates (iso-AE9S) are mixed with a new Gemini cationic surfactant bearing four quaternary ammonium groups (TC-GS). Then, the surface properties and aggregation behavior of the two mixed systems were investigated. The effect of the long polyoxyethylene chains on the conformation and hydration of the hydrophilic head group of AE9C and iso-AE9S weakened their negative charge density, thus hindering their excessive electrostatic adsorption with TC-GS and improving the stability of the mixed systems. The positive synergistic effects of TC-GS/AE9C and TC-GS/iso-AE9S exhibited significantly lower critical micelle concentration, faster diffusion rates, and superior wetting capability compared to single surfactants. The micellization process of both mixed systems is spontaneously enthalpy-driven, and the diffusion-adsorption process is consistent with the mixed diffusion-kinetic mechanism. Finally, both mixed systems are capable of forming complex and interesting aggregate morphologies, with TC-GS/AE9C can form multilayer spherical vesicles and TC-GS/iso-AE9S can form multicompartment concentric spherical vesicles.

Computing Individual Area per Head Group Reveals Lipid Bilayer Dynamics.

Lipid bilayers express a range of phases from solid-like to gel-like to liquid-like as a function of temperature and lipid surface concentration. The area occupied per lipid head group serves as one useful indicator of the bilayer phase, in conjunction with the two-dimensional radial distribution function (i.e., structure factor) within the bilayer. Typically, the area per head group is determined by dividing the bilayer area equally among all head groups. Such an approach is less satisfactory for a multicomponent set of diverse lipids. In this work, area determination is performed on a lipid-by-lipid basis by attributing to a lipid the volume that surrounds each atom. Voronoi tessellation provides this division of the interfacial region on a per-atom basis. The method is applied to a multicomponent system of water, NaCl, and 19 phospholipid types that was devised recently [Langmuir2022, 38, 9481-9499] as a computational representation of the Gram-positive Staphylococcus aureus phospholipid bilayer. Results demonstrate that lipids and water molecules occupy similar extents of area within the interfacial region; ascribing area only to head groups implicitly incorporates assumptions about head group hydration. Results further show that lipid tails provide non-negligible contributions to area on the membrane side of the bilayer-water interface. Results for minimum and maximum area of individual lipids reveal that spontaneous fluctuations displace head groups more than 10 Å from the interfacial region during an NPT simulation at 310 K, leading to a zero contribution to total area at some times. Total area fluctuations and fluctuations per individual lipid relax with a correlation time of ∼10 ns. The method complements density profile as an approach to quantify the structure and dynamics of computational lipid bilayers.

Explicit solvent effects on macromolecular interactions from a solvent-augmented contact value theorem.

The Derjaguin-Landau-Verywey-Overbeek (DLVO) theory has been a remarkably accurate framework for the characterization of macromolecular stability in water solvent. In view of its solvent-implicit nature neglecting the electrostatics of water molecules with non-negligible charge structure and concentration, the precision of the DLVO formalism is somewhat puzzling. In order to shed light on this issue, we derive from our earlier explicit solvent formalism [S. Buyukdagli et al., Phys. Rev. E 87, 063201 (2013)1539-375510.1103/PhysRevE.87.063201] a solvent-augmented contact value theorem and assess the contribution of solvent molecules to the interaction of charged membranes. We find that in the case of hydrophobic membranes with fixed charges embedded in the membrane surface, the nearly exact cancellation of various explicit solvent effects of substantially large magnitude but opposite sign keeps the intermembrane pressure significantly close to the double-layer force of the DLVO theory. Then, in the case of hydrophilic surface charge groups within the aqueous region, due to the spatial separation of the membrane substrate from the location of the fixed charges where the nonlocal dielectric response of the structured solvent is sharply localized, the interfacial field energy and the contact charge densities remain unaffected by the explicit solvent. As a result, the hydration of the lipid head groups suppresses the signature of the solvent molecules from the membrane interaction force.

Hydration Lubrication in Biomedical Applications: From Cartilage to Hydrogels.

ConspectusIn the course of evolution, nature has achieved remarkably lubricated surfaces, with healthy articular cartilage in the major (synovial) joints being the prime example, that can last a lifetime as they slide past each other with ultralow friction (friction coefficient μ = the force to slide surfaces past each other/load compressing the surfaces < 0.01) under physiological pressures (up to 10 MPa or more)). Such properties are unmatched by any man-made materials. The precise mechanism of low friction between such sliding cartilage tissues, which is closely related to osteoarthritis (OA), the most widespread joint disease, affecting hundreds of millions worldwide, has been studied for nearly a century, but is still not fully understood. Traditionally, the roles of load bearing by interstitial fluid within the cartilage bulk and that of thin exuded fluid films at the interface between the sliding cartilage surfaces have been proposed as the main lubrication mechanism. More recent work, however, suggests that molecular boundary layers at the surfaces of articular cartilage and other tissues play a major role in their lubrication. In particular, in recent years hydration lubrication has emerged as a new paradigm for boundary lubrication in aqueous media based on subnanometer hydration shells which massively reduce frictional dissipation. The vectors of hydration lubrication include trapped hydrated ions, hydrated surfactants, biological macromolecules, biomimetic polymers, polyelectrolytes and polyzwitterionic brushes, and close-packed layers of phosphatidylcholine (PC) vesicles, all having in common the exposure of highly hydrated groups at the slip plane. Among them, vesicles (or bilayers) of PC lipids, which are the most widespread lipid class in mammals, are exceptionally efficient lubricating elements as a result of the high hydration of the phosphocholine headgroups they expose. Such lipids are ubiquitous in joints, leading to the proposal that macromolecular surface complexes exposing PC bilayers are responsible for the remarkable lubrication of cartilage. Cartilage, comprising ∼70% water, may be considered to be a complex biological hydrogel, and studying the frictional properties of hydrogels may thus provide new insights into its lubrication mechanisms, leading in turn to novel, highly lubricious hydrogels that may be used in a variety of biomedical and other applications. A better understanding of cartilage lubrication could moreover lead to better treatments for OA, for example, through intra-articular injections of appropriate lubricants or through the creation of low-friction hydrogels that may be used as tissue engineering scaffolds for diseased cartilage.In this Account, we begin by introducing the concept and origin of hydration lubrication, extending from the seminal study of lubrication by hydrated simple ions to more complex systems. We then briefly review different modes of lubrication in synovial joints, focusing primarily on boundary lubrication. We consider modes of hydrogel lubrication and different kinds of such low-friction synthetic gels and then focus on cartilage-inspired, boundary-lubricated hydrogels. We conclude by discussing challenges and opportunities.

Short-chain branched sulfosuccinate as a missing link between surfactants and hydrotropes.

Surfactants aggregate in water into micelles, and these micelles incorporate organic substances to solubilize them. Hydrotropes are compounds that increase the solubility of hydrophobic substances in water without this form of aggregation. Decreasing the chain length of the classical surfactant Aerosol OT (AOT) from C8 to C5 results in a molecule with intermediate properties. Molecular dynamics simulations and surface tension measurements are performed on this short chain derivative of AOT. This compound shows high solubility and at the same time progressive weak aggregation. The hydration of head groups hinders significant plunging into a hydrophobic core, which leads to well defined liquid chain nanodomains. The transition to bicontinuous aggregates is in the concentration range of 1 mol L-1. The sulfonate group of the head groups (placed at the water interface of worm-like aggregates) rather than the aggregate-aggregate interaction is responsible for the unusual small angle X-ray scattering pattern.

Hydration and Hydrogen Bond Order of Octadecanoic Acid and Octadecanol Films on Water at 21 and 1 °C.

The temperature-dependent hydration structure of long-chain fatty acids and alcohols at air-water interfaces has great significance in the fundamental interactions underlying ice nucleation in the atmosphere. We present an integrated theoretical and experimental study of the temperature-dependent vibrational structure and electric field character of the immediate hydration shells of fatty alcohol and acid headgroups. We use a combination of surface-sensitive infrared reflection-absorption spectroscopy (IRRAS), surface potentiometry, and ab initio molecular dynamics simulations to elucidate detailed molecular structures of the octadecanoic acid and octadecanol (stearic acid and stearyl alcohol) headgroup hydration shells at room temperature and near freezing. In experiments, the alcohol at high surface concentration exhibits the largest surface potential; yet we observe a strengthening of the hydrogen-bonding for the solvating water molecules near freezing for both the alcohol and the fatty acid IRRAS experiments. Results reveal that the hydration shells for both compounds screen their polar headgroup dipole moments reducing the surface potential at low surface coverages; at higher surface coverage, the polar headgroups become dehydrated, which reduces the screening, correlating to higher observed surface potential values. Lowering the temperature promotes tighter chain packing and an increase in surface potential. IRRAS reveals that the intra- and intermolecular vibrational coupling mechanisms are highly sensitive to changes in temperature. We find that intramolecular coupling dominates the vibrational relaxation pathways for interfacial water determined by comparing the H2O and the HOD spectra. Using ab initio molecular dynamics (AIMD) calculations on cluster systems of propanol + 6H2O and propionic acid + 10H2O, a spectral decomposition scheme was used to correlate the OH stretching motion with the IRRAS spectral features, revealing the effects of intra- and intermolecular coupling on the spectra. Spectra calculated with AIMD reproduce the red shift and increase in intensity observed in experimental spectra corresponding to the OH stretching region of the first solvation shell. These findings suggest that intra- and intermolecular vibrational couplings strongly impact the OH stretching region at fatty acid and fatty alcohol water interfaces. Overall, results are consistent with ice templating behavior for both the fatty acid and the alcohol, yet the surface potential signature is strongest for the fatty alcohol. These findings develop a better understanding of the complex surface potential and spectral signatures involved in ice templating.

Structural Characterization of Nonionic Surfactant Micelles with CO2/Ethylene Oxide Head Groups and Their Temperature Dependence.

Using CO2 as a resource in the production of materials is a viable alternative to conventional, petroleum-based raw materials and therefore offers great potential for more sustainable chemistry. This study presents a detailed structural characterization of aggregates of nonionic dodecyl surfactants with different amounts of CO2 substituting ethylene oxide (EO) in the head group. The micellar structure was characterized as a function of concentration and temperature by dynamic and static light scattering and, in further detail, by small-angle neutron scattering (SANS). The influence of the CO2 unit in the hydrophilic EO group is systematically compared to the incorporation of propylene oxide (PO) and propiolactone (PL). The surfactants with carbonate groups in their head groups form ellipsoidal micelles in an aqueous solution similar to conventional nonionic surfactants, becoming bigger with increasing CO2 content. In contrast, the incorporation of PO units hardly alters the behavior, while the incorporation of a PL unit has an effect comparable to the CO2 unit. The analysis of the SANS data shows decreasing hydration with increasing CO2 and PL content. By increasing the temperature, a typical sphere-rod transition is observed, where CO2 surfactants show a much higher elongation with increasing temperature, which is correlated with the reduced cloud point and a lower extent of head group hydration. Our findings demonstrate that CO2-containing surface-active compounds are an interesting, potentially "greener" alternative to conventional nonionic surfactants.

Erratum: Neutron Spin Echo Spectroscopy as a Unique Probe for Lipid Membrane Dynamics and Membrane-Protein Interactions.

Erratum: Neutron Spin Echo Spectroscopy as a Unique Probe for Lipid Membrane Dynamics and Membrane-Protein Interactions.

Structure and Interdigitation of Chain-Asymmetric Phosphatidylcholines and Milk Sphingomyelin in the Fluid Phase.

We addressed the frequent occurrence of mixed-chain lipids in biological membranes and their impact on membrane structure by studying several chain-asymmetric phosphatidylcholines and the highly asymmetric milk sphingomyelin. Specifically, we report trans-membrane structures of the corresponding fluid lamellar phases using small-angle X-ray and neutron scattering, which were jointly analyzed in terms of a membrane composition-specific model, including a headgroup hydration shell. Focusing on terminal methyl groups at the bilayer center, we found a linear relation between hydrocarbon chain length mismatch and the methyl-overlap for phosphatidylcholines, and a non-negligible impact of the glycerol backbone-tilting, letting the sn1-chain penetrate deeper into the opposing leaflet by half a CH2 group. That is, penetration-depth differences due to the ester-linked hydrocarbons at the glycerol backbone, previously reported for gel phase structures, also extend to the more relevant physiological fluid phase, but are significantly reduced. Moreover, milk sphingomyelin was found to follow the same linear relationship suggesting a similar tilt of the sphingosine backbone. Complementarily performed molecular dynamics simulations revealed that there is always a part of the lipid tails bending back, even if there is a high interdigitation with the opposing chains. The extent of this back-bending was similar to that in chain symmetric bilayers. For both cases of adaptation to chain length mismatch, chain-asymmetry has a large impact on hydrocarbon chain ordering, inducing disorder in the longer of the two hydrocarbons.

Semi-automated Optimization of the CHARMM36 Lipid Force Field to Include Explicit Treatment of Long-Range Dispersion.

The development of the CHARMM lipid force field (FF) can be traced back to the early 1990s with its current version denoted CHARMM36 (C36). The parametrization of C36 utilized high-level quantum mechanical data and free energy calculations of model compounds before parameters were manually adjusted to yield agreement with experimental properties of lipid bilayers. While such manual fine-tuning of FF parameters is based on intuition and trial-and-error, automated methods can identify beneficial modifications of the parameters via their sensitivities and thereby guide the optimization process. This work introduces a semi-automated approach to reparametrize the CHARMM lipid FF with consistent inclusion of long-range dispersion through the Lennard-Jones particle-mesh Ewald (LJ-PME) approach. The optimization method is based on thermodynamic reweighting with regularization with respect to the C36 set. Two independent optimizations with different topology restrictions are presented. Targets of the optimizations are primarily liquid crystalline phase properties of lipid bilayers and the compression isotherm of monolayers. Pair correlation functions between water and lipid functional groups in aqueous solution are also included to address headgroup hydration. While the physics of the reweighting strategy itself is well-understood, applying it to heterogeneous, complex anisotropic systems poses additional challenges. These were overcome through careful selection of target properties and reweighting settings allowing for the successful incorporation of the explicit treatment of long-range dispersion, and we denote the newly optimized lipid force field as C36/LJ-PME. The current implementation of the optimization protocol will facilitate the future development of the CHARMM and related lipid force fields.

Lipid-Bilayer Assemblies on Polymer-Bearing Surfaces: The Nature of the Slip Plane in Asymmetric Boundary Lubrication.

Phospholipid–macromolecule complexes have been proposed to form highly efficient, lubricating boundary layers at artificial soft surfaces or at biological surfaces such as articular cartilage, where the friction reduction is attributed to the hydration lubrication mechanism acting at the exposed, hydrated head groups of the lipids. Here we measure, using a surface force balance, the normal and frictional interactions between model mica substrates across several different configurations of phosphatidylcholine (PC) lipid aggregates and adsorbed polymer (PEO) layers, to provide insight into the nature of such lubricating boundary layers in both symmetric and especially asymmetric configurations. Our results reveal that, irrespective of the configuration, the slip plane between the sliding surfaces reverts wherever possible to a bilayer–bilayer interface where hydration lubrication reduces the friction strongly. Where such an interface is not available, the sliding friction remains high. These findings may account for the low friction observed between both biological and synthetic hydrogel surfaces which may be asymmetrically coated with lipid-based boundary layers and fully support the hydration lubrication mechanism attributed to act at such boundary layers.

Lipid membranes exposed to dispersions of phytantriol and monoolein cubosomes: Langmuir monolayer and HeLa cell membrane studies

The interactions of liquid-crystalline nanoparticles based on lipid-like surfactants, glyceryl monooleate, monoolein (GMO) and 1,2,3-trihydroxy-3,7,11,15-tetramethylhexadecane, phytantriol (PT) with selected model lipid membranes prepared by Langmuir technique were compared. Monolayers of DPPC, DMPS and their mixture DPPC:DMPS 87:13 mol% were used as simple models of one leaflet of a cell membrane. The incorporation of cubosomes into the lipid layers spread at the air-water interface was followed by surface-pressure measurements and Brewster angle microscopy. The cubosome - membrane interactions lead to the fluidization of the model membranes but this effect depended on the composition of the model membrane and on the type of cubosomes. The interactions of PT cubosomes with lipid layers, especially DMPS-based monolayer were stronger compared with those of GMO-based nanoparticles. The kinetics of incorporation of cubosomal material into the lipid layer was influenced by the extent of hydration of the polar headgroups of the lipid: faster in the case of smaller, less hydrated polar groups of DMPS than for strongly hydrated uncharged choline of DPPC. The membrane disrupting effect of cubosomes increased at longer times of the lipid membrane exposure to the cubosome solution and at larger carrier concentrations. Langmuir monolayer observations correspond well to results of studies of HeLa cells exposed to cubosomes. The larger toxicity of PT cubosomes was confirmed by MTS. Their ability to disrupt lipid membranes was imaged by confocal microscopy. On the other hand, PT cubosomes easily penetrated cellular membranes and released cargo into various cellular compartments more effectively than GMO-based nanocarriers. Therefore, at low concentrations, they may be further investigated as a promising drug delivery tool.

Interfacial and Foaming Properties of Tailor-Made Glycolipids-Influence of the Hydrophilic Head Group and Functional Groups in the Hydrophobic Tail.

Glycolipids are a class of biodegradable surfactants less harmful to the environment than petrochemically derived surfactants. Here we discuss interfacial properties, foam stability, characterized in terms of transient foam height, gas volume fraction and bubble diameter as well as texture of seven enzymatically synthesized surfactants for the first time. Glycolipids consisting of different head groups, namely glucose, sorbitol, glucuronic acid and sorbose, combined with different C10 acyl chains, namely decanoate, dec-9-enoate and 4-methyl-nonanoate are compared. Equilibrium interfacial tension values vary between 24.3 and 29.6 mN/m, critical micelle concentration varies between 0.7 and 3.0 mM. In both cases highest values were found for the surfactants with unsaturated or branched tail groups. Interfacial elasticity and viscosity, however, were significantly reduced in these cases. Head and tail group both affect foam stability. Foams from glycolipids with sorbose and glucuronic acid derived head groups showed higher stability than those from surfactants with glucose head group, sorbitol provided lowest foam stability. We attribute this to different head group hydration also showing up in the time to reach equilibrium interfacial adsorption. Unsaturated tail groups reduced whereas branching enhanced foam stability compared to the systems with linear, saturated tail. Moreover, the tail group strongly influences foam texture. Glycolipids with unsaturated tail groups produced foams quickly collapsing even at smallest shear loads, whereas the branched tail group yielded a higher modulus than the linear tails. Normalized shear moduli for the systems with different head groups varied in a narrow range, with the highest value found for decylglucuronate.