Hydrophilic Phospholipid Research Articles

Molecular insights into the resistance of phospholipid heads to the membrane penetration of graphene nanosheets.

The interaction between nanomaterials and phospholipid membranes underlies many emerging biological applications. To what extent hydrophilic phospholipid heads shield the bilayer from the integration of hydrophobic nanomaterials remains unclear, and this open question contains important insights for understanding biological membrane physics. Here, we present molecular dynamics (MD) simulations to clarify the resistance of phospholipid heads to the membrane penetration of graphene nanosheets. With 130 simulation trials, we observed that ∼22% graphene nanosheets penetrate the POPC bilayer. Sharp corners of the nanosheets should have a lower energy barrier than nanosheet edges, but interestingly, the membrane penetration mainly starts from the edge-approaching orientation. We thoroughly analyzed the pentration pathway and propulsion, indicating that the membrane penetration of graphene nanosheets is dominated by the joint effects of nanosheet edges and corners. Furthermore, the molecular origin of the resistance is clarified by evaluating the bilayers of different phospholipids, which successfully correlates the penetration resistance of phospholipid heads with the correlated motions of neighboring phospholipids for the first time. These results are expected to inspire future studies on the dynamic behavior of phospholipids, bio-nano interfaces, and design of biological nanomaterials.

Ovine plasma dipalmitoylphosphatidylcholine does not predict decompression bubbling

Decompression illness (DCI) is the main risk associated with scuba diving. Some divers (“bubblers”) are more sensitive to DCI than others (“non-bubblers”). We found that there are active hydrophobic spots (AHS) on the luminal aspect of ovine blood vessels, which contain the surfactant dipalmitoylphosphatidylcholine (DPPC). DPPC leaks from the lung into the plasma, settling on the blood vessel to create AHS. These are the main source of gas micronuclei from which bubbles develop after decompression. A correlation between bubbling ovine blood vessels and the animal's plasma DPPC might lead to the development of a blood test for vulnerability to DCI. Samples from ovine blood vessels were stretched on microscope slides, placed anaerobically in saline at the bottom of a Pyrex bowl, and exposed to high pressure. Automated photography was used after decompression to reveal AHS by visualising their bubble production. Phospholipids were extracted from the AHS and plasma for determination of DPPC. Bubbling was unrelated to the concentration of DPPC in the plasma (2.15 ± 0.87 μg/ml). Bubble production from the AHS (n = 130) as a function of their DPPC content yielded two groups, one unrelated to DPPC and the other which demonstrated increased bubbling with elevation of DPPC. We suggest this may be related to alternate layering with hydrophobic and hydrophilic phospholipids. This study reinforces the connection between DPPC and DCI. However, a blood test for diver vulnerability to decompression stress is not recommended.

Preservation of orange juice using propolis.

Orange juice is one of the most popular and the most consumed fruit juices all over the world, especially in Europe and the chemical food preservatives, such as sodium benzoate, potassium sorbate and their mixtures, have long been used in orange juice sold on the market. Excessive consumption of these preservatives may be hazardous to human health. Propolis, composed of resins collected from plant buds and exudates and mixed with salivary gland secretions and beeswax by honey bee workers, has been used as a human medicine and natural food preservative. We hypothesis that propolis, without alcohol, can serve as an alternative and non-synthetic preservative of orange juice. In this study, the preservative effect of propolis emulsion on orange juice was determined up to 35days. Propolis emulsion (0.02g/mL propolis, 12mL), emulsion control (12mL containing Tween-80, hydrophilic phospholipid and polyethylene glycol 400), sodium benzoate (0.4g) and potassium sorbate (0.4g) was each added to 388, 388, 400 and 400mL orange juice respectively. Propolis emulsion showed significant inhibition of bacteria growth and l-ascorbic acid degradation. Orange juice pH value, titratable acidity, total phenolic content, color and antioxidant capacity were effectively maintained by propolis emulsion. A control solution with all the same emulsifying agents without propolis did not show these properties. It was concluded that propolis can be used as a natural additive agent in orange juice or other fruit juices as an alternative to chemical preservatives.

Photosensitive nanocapsules for use in imaging from poly(styrene-co-divinylbenzene) cross-linked with coumarin derivatives

The study objective was to generate biocompatible probes and develop a stable macromolecule imaging system that are based on nanolipopolymersomes and can be used in living cells. We synthesized nanolipopolymersomes with a fluorescent polymer wall surrounded by an outer phospholipid shell that exhibits potential for the controlled delivery of diagnostic agents to cells. We describe a new type of probe suitable for dual detection methods (spectrophotometric and fluorescence). This aspect makes it unique among currently available probes because allows it to be detected with greater accuracy. We developed a highly fluorescent coumarinated polymer to overcome the limited brightness of conventional dyes with insufficient for long-term photostablility. Hydrophilic dyes (Lucifer yellow, Procion red, Procion blue) are entrapped in the aqueous core of stable polymeric nanocapsules with coumarin 6 embedded in a nanometre-thick poly(styrene-co-divinylbenzene) wall. Target compounds can be incorporated into nanocapsules in a single step. The hydrophilic phospholipids outer shell ensures biocompatibility and facilitates cell penetration. In this way, the novel fluorescent hybrid materials can help of nanotechnology.

Rational Design of Membrane Proximal External Region Lipopeptides Containing Chemical Modifications for HIV-1 Vaccination

The inability to generate broadly neutralizing antibody (bnAb) responses to the membrane proximal external region (MPER) of HIV-1 gp41 using current vaccine strategies has hampered efforts to prevent the spread of HIV. To address this challenge, we investigated a novel hypothesis to help improve the anti-MPER antibody response. Guided by structural insights and the unique lipid reactivity of anti-MPER bnAbs, we considered whether amino acid side chain modifications that emulate hydrophilic phospholipid head groups could contribute to the generation of 2F5-like or 4E10-like neutralizing anti-MPER antibodies. To test this hypothesis, we generated a series of chemically modified MPER immunogens through derivatization of amino acid side chains with phosphate or nitrate groups. We evaluated the binding affinity of the chemically modified peptides to their cognate monoclonal antibodies, 2F5 and 4E10, using surface plasmon resonance. The modifications had little effect on binding to the antibodies and did not influence epitope secondary structure when presented in liposomes. We selected five of the chemically modified sequences to immunize rabbits and found that an immunogen containing both the 2F5 and 4E10 epitopes and a phosphorylated threonine at T676 elicited the highest anti-peptide IgG titers, although the high antipeptide titers did not confer higher neutralizing activity. These data indicate that side chain modifications adjacent to known neutralizing antibody epitopes are capable of eliciting antibody responses to the MPER but that these chemically modified gp41 epitopes do not induce neutralizing antibodies.

Molecular Modeling of Domain Formation upon Protein Adsorption in Lipid Bilayers

The mechanisms that govern domain formation in phospholipid bilayers are unclear. Understanding the underlying principles of domain formation in model lipid bilayers will provide with insights on how protein adsorption leads to domain formation and also will lead to the effective design of novel biotechnology applications that can take advantage of the structure to function relationship in biology. In this work, the thermodynamics and structural properties of domain formation upon protein adsorption in model lipid membranes are studied through the application of a three dimensional molecular theory that includes a complete description of the relevant interactions of the entire phospholipid molecules. This theoretical approach takes into account the electrostatic interactions of the hydrophilic phospholipid headgroups as well as the attractive packing interactions of the phospholipid acyl tails. The proposed theory considers in an explicit manner the molecular conformations, size, shape and charge density of each molecule within a mean-field level approximation for the intermolecular interactions. The results show how domain formation in lipid bilayers depends on several biologically relevant environments such as different salt concentrations, solution pH and phospholipid composition of the bilayer, i.e. , the chemical structure and number density of the different phospholipid molecules present in the bilayer. The molecular theory provides with the tools for understanding the fundamental principles of phospholipid domain formation by giving insights on how the membrane responds to changes in its chemical environment. Moreover, since the theory includes an explicit description of the phospholipid headgroups, the coupling between the physical states of the two leaflets of the bilayer as the result of protein adsorption onto one side of the bilayer is also described.

Differential Effects of Lysophosphatidic Acid and Phosphatidylinositol 4,5-Bisphosphate on Actin Dynamics by Direct Association with the Actin-binding Protein Villin

We have previously reported that the epithelial cell-specific actin-binding protein villin directly associates with phosphatidylinositol 4,5-bisphosphate (PIP(2)) through three binding sites that overlap with actin-binding sites in villin. As a result, association of villin with PIP(2) inhibits actin depolymerization and enhances actin cross-linking by villin. In this study, we demonstrate that these three PIP(2)-binding sites also bind the more hydrophilic phospholipid, lysophosphatidic acid (LPA) but with a higher affinity than PIP(2) (dissociation constant (K(d)) of 22 mum versus 39.5 mum for PIP(2)). More interestingly, unlike PIP(2), the association of villin with LPA inhibits all actin regulatory functions of villin. In addition, unlike PIP(2), LPA dramatically stimulates the tyrosine phosphorylation of villin by c-Src kinase. These studies suggest that in cells, selective interaction of villin with either PIP(2) or LPA could have dramatically different outcomes on actin reorganization as well as phospholipid-regulated cell signaling. These studies provide a novel regulatory mechanism for phospholipid-induced changes in the microfilament structure and cell function and suggest that LPA could be an intracellular regulator of the actin cytoskeleton.

Neutron and X-ray Scattering on the Monolayer Structure of a Lecithin Fullerene-Derivative

Using neutron reflectivity with contrast variation, X-ray reflectivity, and grazing incident small-angle X-ray scattering (GISAXS), we have characterized the in-depth and in-plane structural characteristics of the Langmuir and Langmuir-Blodgett (LB) films formed by a novel lecithin C60-derivative, FPTL, of three phospholipids jointly bonded on one single olefinic moiety of a C60 cage. Based on the neutron reflectivity measured, we have proposed a monolayer structure, with the C60 cages of FPTL lifted into the air and hydrophilic phospholipid heads immersed in water, for the FPTL Langmuir layer formed on water. On the other hand, the LB film of FPTL prepared on mica exhibits clear Kiessig fringes in the X-ray reflectivity profile, indicating a 27 angstroms monolayer film with less molecular orientation. With GISAXS, we have extracted an in-plane correlation length of about 210 A for a possible in-plane aggregation of C60 of FPTL in the LB monolayer. We have also demonstrated the highly ordered monolayer structures of a lecithin lipid, in elucidating the positive effect of the attached functional group-phospholipids on the monolayer formation of the lecithin C60-derivative.

Correlation of trimethoprim and brodimoprim physicochemical and lipid membrane interaction properties with their accumulation in human neutrophils.

Dipalmitoylphosphatidylcholine vesicles were used as a biological membrane model to investigate the interaction and the permeation properties of trimethoprim and brodimoprim as a function of drug protonation. The drug-membrane interaction was studied by differential scanning calorimetry. Both drugs interacted with the hydrophilic phospholipid head groups when in a protonated form. An experiment on the permeation of the two drugs through dipalmitoylphosphatidylcholine biomembranes showed higher diffusion rate constants when the two drugs were in the uncharged form; lowering of the pH (formation of protonated species) caused a reduction of permeation. Drug uptake by human neutrophil cells was also investigated. Both drugs may accumulate within neutrophils; however, brodimoprim does so to a greater extent. This accumulation is probably due to a pH gradient driving force, which allows the two drugs to move easily from the extracellular medium (pH approximately 7.3) into the internal cell compartments (acid pH). Once protonated, both drugs are less able to permeate and can be trapped by the neutrophils. This investigation showed the importance of the physicochemical properties of brodimoprim and trimethoprim in determining drug accumulation and membrane permeation pathways.

Preparation of Phospholipid Polylners and Their Properties as Polymer Hydrogel Membranes

A methacrylate monomer having the phospholipid polar group, 2-methacryloyloxyethyl phosphorylcholine (MPC) was prepared by an improved method with good yield. MPC was copolymerized with n-butyl methacrylate (BMA). The polymer membranes were prepared from the poly(MPC-co-BMA) by a solution casting method. The membrane adsorbed water well and became a hydrogel structure even MPC mole fraction in the copolymer was 0.04. The water content of the hydrogel membrane increased with increase of MPC units and rise of temperature. These properties of the hydrogel membrane were attributed to the highly hydrophilic phospholipid polar group in the copolymer. Water soluble organic compounds and proteins whose molecular weights were below 104 permeated through the hydrogel membrane. However, the protein could not permeate when the molecular weight was higher than 105.

The relation of lipids to the mineral components in salivary calculi

Using lipid histochemical and microradiographic methods, the distribution of lipids and the inorganic component in different areas of salivary calculi was investigated. Two main groups of lipids were found, i.e. hydrophilic phospholipids and hydrophobic lipids. The hydrophilic phospholipids were shown to be composed mainly of phosphosphingosides and of the hydrophobic lipids cholesterol was demonstrated. Phosphosphingosides were localized in more or less lamellar zones as also in large homogeneous areas. In some cases the calculi were surrounded by a structureless non-mineralized zone exhibiting a strongly positive reaction for phosphosphingosides. Cholesterol was found in isolated band-formed areas. Phosphosphingosides and cholesterol were especially prevalent in areas showing a low or slight degree of mineralization. In areas showing a high degree of mineralization the corresponding lipids gave a weak or absent histochemical reaction. After EDTA-decalcification, however, an increase in the concentration of lipid was noticed in high mineralized areas, indicating a masking process. The influence of various factors on the presence and distribution of different lipids was discussed.