Molecular Structure of the Dioctadecyldimethylammonium Bromide (DODAB) Bilayer

Dioctadecyldimethylammonium bromide (DODAB) is a double-chained quaternary ammonium surfactant that assembles in water into bilayer structures. This letter reports the molecular dynamics (MD) computer simulations of the DODAB bilayer at 25 °C. The simulations show that the surfactant membrane arranges spontaneously into the rippled phase (Pβ’) at that temperature. The ordering within the chain fragment closest to the hydrophilic head (carbon atoms 1−5) is relatively low. It grows significantly for the carbon atoms located in the center of the membrane (atoms 6−17). The C6−C17 chain fragments are well aligned and tilted by ca. 15° with respect to the bilayer normal

Porphyrin–Nanoclay Photosensitizers for Visible Light Induced Oxidation of Phenol in Aqueous Media

A new type of hybrid photosensitizer (Po–C30B) was obtained by efficient adsorption of a 5,10,15,20-tetrakis­(4-carboxyphenyl)­porphyrin (Po) by Cloisite 30B (C30B)a monotallow bis­(hydroxyethyl)­ammonium-modified montmorillonite clayfrom acidic solution in methanol. Structural and spectroscopic properties of Po-nanoclay photosensitizer were determined using X-ray diffraction, laser scanning fluorescence confocal microscopy, and electronic absorption/emission spectroscopies. Po is present not only at the surface of the nanoclay but also in the interior of the Po-C30B hybrid material. The obtained material was found to be an efficient photosensitizer for the oxidation of phenol in aqueous solution under irradiation with the visible light (λ > 470 nm). The mechanism and the quantum yield of that process were shown to be strongly pH-dependent. They were controlled by the acid–base equilibria of porphyrin associated with imine N-protonation as well as by the ionization of the phenol molecule. The quantitative information regarding these dependencies was obtained. The values of K3 and K4 acid–base equilibrium constants were determined (pK3 = 5.88 and pK4 = 2.46) from the absorption spectra recorded during acid–base titration and using an evolutionary factor analysis with the mathematical model including dicationic (H2Po2+), monocationic (HPo+), and neutral (Po) porphyrin forms. They were used to evaluate the importance of these forms in singlet oxygen generation by Po–C30B under defined pH conditions. Moreover, the hybrid photosensitizer can be used repeatedly, which makes it possible to use it in industrial applications

Deciphering Lipid Arrangement in Phosphatidylserine/Phosphatidylcholine Mixed Membranes: Simulations and Experiments

Phosphatidylserine (PS) exposure on the plasma membrane is crucial for many cellular processes including apoptotic cell recognition, blood clotting regulation, cellular signaling, and intercellular interactions. In this study, we investigated the arrangement of PS headgroups in mixed PS/phosphatidylcholine (PC) bilayers, serving as a simplified model of the outer leaflets of mammalian cell plasma membranes. Combining atomistic-scale molecular dynamics (MD) simulations with Langmuir monolayer experiments, we unraveled the mutual miscibility of POPC and POPS lipids and the intricate intermolecular interactions inherent to these membranes as well as the disparities in position and orientation of PC and PS headgroups. Our experiments revealed micrometer-scale miscibility at all mole fractions of POPC and POPS, marked by modest deviations from ideal mixing with no apparent microscale phase separation. The MD simulations, meanwhile, demonstrated that these deviations were due to strong electrostatic interactions between like-lipid pairs (POPC–POPC and POPS–POPS), culminating in lateral segregation and nanoscale clustering. Notably, PS headgroups profoundly affect the ordering of the lipid acyl chains, leading to lipid elongation and subtle PS protrusion above the zwitterionic membrane. In addition, PC headgroups are more tilted with respect to the membrane normal, while PS headgroups align at a smaller angle, making them more exposed to the surface of the mixed PC/PS membranes. These findings provide a detailed molecular-level account of the organization of mixed PC/PS membranes, corroborated by experimental data. The insights gained here extend our comprehension of the physiological role of PSs

Interactions of a Hydrophobically Modified Polycation with Zwitterionic Lipid Membranes

The interactions between synthetic polycations and phospholipid bilayers play an important role in some biophysical applications such as gene delivery or antibacterial usage. Despite extensive investigation into the nature of these interactions, their physical and molecular bases remain poorly understood. In this Article, we present the results of our studies on the impact of a hydrophobically modified strong polycation on the properties of a zwitterionic bilayer used as a model of the mammalian cellular membrane. The study was carried out using a set of complementary experimental methods and molecular dynamic (MD) simulations. A new polycation, poly(allyl-N,N-dimethyl-N-hexylammonium chloride) (polymer 3), was synthesized, and its interactions with liposomes composed of 2-oleoyl-1-palmitoyl-sn-glycero-3-phosphocholine (POPC) were examined using dynamic light scattering (DLS), zeta potential measurements, and cryo-transmission electron microscopy (cryo-TEM). Our results have shown that polymer 3 can efficiently associate with and insert into the POPC membrane. However, it does not change its lamellar structure, as was demonstrated by cryo-TEM. The influence of polymer 3 on the membrane functionality was studied by leakage experiments applying a fluorescence dye (calcein) encapsulated in the phospholipid vesicles. The MD simulations of model systems reveal that polymer 3 promotes formation of hydrophilic pores in the membrane, thus increasing considerably its permeability

Properties of Polyethylene Glycol Supported Tetraarylporphyrin in Aqueous Solution and Its Interaction with Liposomal Membranes

5,10,15,20-Tetrakis(4-hydroxyphenyl)porphyrin was functionalized by covalent attachment of poly(ethylene glycol) (PEG) chains of various molecular weights, 350, 2000, and 5000 Da. The properties of PEG-functionalized tetraarylporphyrins in aqueous solution and their interactions with liposomes have been studied. Electronic absorption spectroscopy, dynamic light scattering, atomic force microscopy, and fluorescence quenching were used to monitor aggregation of porphyrin chromophores and behavior of the attached PEG chains in the aqueous solution. The tendency for aggregation of porphyrin chromophores in aqueous solution and the efficiency of fluorescence quenching by KI decrease with increasing length of PEG chain linked to the porphyrin ring. The experimental results indicate that polymer clusters are present in aqueous solution of all pegylated porphyrins. The interactions between the pegylated porphyrins and phosphatidylcholine liposomes in the aqueous solution were studied using the fluorescence methods. The apparent binding constants of porphyrin chromophores to liposomes were determined. The degree of binding was found to be dependent on the molecular weight of the attached polymer

Molecular Insight into Drug-Loading Capacity of PEG–PLGA Nanoparticles for Itraconazole

Nanoparticles made of amphiphilic block copolymers comprising biodegradable core-forming blocks are very attractive for the preparation of drug-delivery systems with sustained release. Their therapeutic applications are, however, hindered by low values of the drug-loading content (DLC). The compatibility between the drug and the core-forming block of the copolymer is considered the most important factor affecting the DLC value. However, the molecular picture of the hydrophobic drug–copolymer interaction is still not fully recognized. Herein, we examined this complex issue using a range of experimental techniques in combination with atomistic molecular dynamics simulations. We performed an analysis of the interaction between itraconazole, a model hydrophobic drug, and a poly­(ethylene glycol)–poly­(lactide-<i>co</i>-glycolide) (PEG–PLGA) copolymer, a biodegradable copolymer commonly used for the preparation of drug-delivery systems. Our results clearly show that the limited capacity of the PEG–PLGA nanoparticles for the accumulation of hydrophobic drugs is due to the fact that the drug molecules are located only at the water–polymer interface, whereas the interior of the PLGA core remains empty. These findings can be useful in the rational design and development of amphiphilic copolymer-based drug-delivery systems

Endothelium in Spots – High-Content Imaging of Lipid Rafts Clusters in db/db Mice

<div><p>Lipid rafts (LRs) are dynamic, sterol- and sphingolipid-enriched nanodomains involved in the regulation of cellular functions and signal transduction, that upon stimuli, <i>via</i> (e.g. association of raft proteins and lipids), may cluster into domains of submicron or micron scale. Up to date, however, lipid raft clusters were observed only under artificially promoted conditions and their formation <i>in vivo</i> has not been confirmed. Using non-destructive approach involving Raman and Atomic Force Microscopy imaging we demonstrated the presence of clustered lipid rafts in endothelium of the aorta of the db/db mice that represent a reliable murine model of type 2 diabetes. The raft clusters in the aorta of diabetic mice were shown to occupy a considerably larger (about 10-fold) area of endothelial cells surface as compared to the control. Observation of pathology-promoted LRs confirms that the cellular increase of lipid content results in clustering of LRs. Clustering of LRs leads to the formation of assemblies with diameters up to 3 micrometers and increased lipid character. This massive clustering of lipid rafts in diabetes may trigger a signaling cascade leading to vascular inflammation.</p></div

Behavior of 2,6-Bis(decyloxy)naphthalene Inside Lipid Bilayer

Interactions between small organic molecules and lipid or cell membranes are important because of their role in the distribution of biologically active substances inside the membrane and their permeation through the cell membranes. In the current paper, we have explored the effect of the attachment of long hydrocarbon tails on the behavior of small organic molecule inside the lipid membrane. Naphthalene with two decyloxy groups attached at the opposite sites of the ring (2,6-bis(decyloxy)naphthalene, 3) was synthesized and incorporated into phosphatidylcholine (PC) vesicles. Fluorescence methods as well as molecular dynamic (MD) simulations were used to estimate the position, orientation, and migration of compound 3 in PC bilayer. It was found that the naphthalene ring of compound 3 resides in the upper acyl chain region of the bilayer and the hydrocarbon tails are directed to the center of the bilayer. As was shown with cryotransmission electron microscopy (cryo-TEM), such lipidlike conformation enables compound 3 to be incorporated into liposomes at a very high content without their disintegration. Moreover, compound 3 can migrate from one leaflet to other. The mechanism of this process is, however, different from that characteristic of the flip-flop event of lipid molecules in the membrane. Finally, the possible application of compound 3 as a rotational molecular probe for monitoring fluidity of liposomal membrane in the acyl side chain region was checked by studies of the effect of cholesterol on the fluorescence anisotropy of 3

Size statistics of clustered lipid rafts in T2DM.

<p>The x (<b>A</b>), y (<b>B</b>) and z (<b>C</b>) dimensions of LRs observed for 16-weeks-old (black) and 20-weeks-old (red) mice determined based on the acquired AFM topography images (the example in <b>D</b>: a representative topography image along with a topography cross-section) and the summary of statistical data related to the LRs size (<b>E</b>).</p