Heterogeneous Rate Constant for Amorphous Silica Nanoparticle Adsorption on Phospholipid Monolayers.

The interaction of amorphous silica nanoparticles with phospholipid monolayers and bilayers has received a great deal of interest in recent years and is of importance for assessing potential cellular toxicity of such species, whether natural or synthesized for the purpose of nanomedical drug delivery and other applications. This present communication studies the rate of silica nanoparticle adsorption on to phospholipid monolayers in order to extract a heterogeneous rate constant from the data. This rate constant relates to the initial rate of growth of an adsorbed layer of nanoparticles as SiO2 on a unit area of the monolayer surface from unit concentration in dispersion. Experiments were carried out using the system of dioleoyl phosphatidylcholine (DOPC) monolayers deposited on Pt/Hg electrodes in a flow cell. Additional studies were carried out on the interaction of soluble silica with these layers. Results show that the rate constant is effectively constant with respect to silica nanoparticle size. This is interpreted as indicating that the interaction of hydrated SiO2 molecular species with phospholipid polar groups is the molecular initiating event (MIE) defined as the initial interaction of the silica particle surface with the phospholipid layer surface promoting the adsorption of silica nanoparticles on DOPC. The conclusion is consistent with the observed significant interaction of soluble SiO2 with the DOPC layer and the established properties of the silica-water interface.

Molecular allergology approach to allergic asthma.

Allergic asthma is a frequently encountered and well described asthma phenotype. However, its precise mechanisms are less known. The tools for targeted selection of patients for an optimal response to intervention (prevention or treatment) are also lacking. Here we explore the potential of the molecular allergology approach to achieve a better understanding of allergic asthma mechanisms, a precise diagnosis and an optimal management of these patients.

Structure and Dynamics of Dioleoyl-Phosphatidylcholine Bilayers under the Influence of Quercetin and Rutin.

Quercetin and rutin, two widely studied flavonoids with applications foreseen in the sectors of pharmaceutical and cosmetic industries, have been chosen as model compounds for a detailed structural and dynamical investigation onto their influence on fluid lipid bilayers. Combining global small angle X-ray scattering analysis with molecular dynamics, various changes in the properties of dioleoyl-phosphatidylcholine (DOPC) bilayers have been determined. The solubility of quercetin in DOPC membranes is assured up to 12 mol %, whereas rutin, with additional glucose and rhamnose groups, are fully soluble only up to 6 mol %. Both flavonoids induce an increase in membrane undulations and thin the bilayers slightly (<1 Å) in a concentration dependent manner, wherein quercetin shows a stronger effect. Concomitantly, in the order of 2-4%, the adjacent bilayer distance increases with the flavonoid's concentration. Partial molecular areas of quercetin and rutin are determined to be 26 and 51 Å2, respectively. Simulated averaged areas per molecule confirm these estimates. A 60° tilted orientation of quercetin is observed with respect to the bilayer normal, whereas the flavonoid moiety of rutin is oriented more perpendicular (α-angle 30°) to the membrane surface. Both flavonoid moieties are located at a depth of 12 and 16 Å for quercetin and rutin, respectively, while their anionic forms display a location closer to the polar interface. Finally, at both simulated concentrations (1.5 and 12 mol %), DOPC-rutin systems induce a stronger packing of the pure DOPC lipid bilayer, mainly due to stronger attractive electrostatic interactions in the polar lipid head region.

Exploring the biophysical properties of phytosterols in the plasma membrane for novel cancer prevention strategies.

Cancer is a global problem with no sign that incidences are reducing. The great costs associated with curing cancer, through developing novel treatments and applying patented therapies, is an increasing burden to developed and developing nations alike. These financial and societal problems will be alleviated by research efforts into prevention, or treatments that utilise off-patent or repurposed agents. Phytosterols are natural components of the diet found in an array of seeds, nuts and vegetables and have been added to several consumer food products for the management of cardio-vascular disease through their ability to lower LDL-cholesterol levels. In this review, we provide a connected view between the fields of structural biophysics and cellular and molecular biology to evaluate the growing evidence that phytosterols impair oncogenic pathways in a range of cancer types. The current state of understanding of how phytosterols alter the biophysical properties of plasma membrane is described, and the potential for phytosterols to be repurposed from cardio-vascular to oncology therapeutics. Through an overview of the types of biophysical and molecular biology experiments that have been performed to date, this review informs the reader of the molecular and biophysical mechanisms through which phytosterols could have anti-cancer properties via their interactions with the plasma cell membrane. We also outline emerging and under-explored areas such as computational modelling, improved biomimetic membranes and ex vivo tissue evaluation. Focus of future research in these areas should improve understanding, not just of phytosterols in cancer cell biology but also to give insights into the interaction between the plasma membrane and the genome. These fields are increasingly providing meaningful biological and clinical data but iterative experiments between molecular biology assays, biosynthetic membrane studies and computational membrane modelling improve and refine our understanding of the role of different sterol components of the plasma membrane.

Experimental Modeling of Flavonoid-Biomembrane Interactions.

Nonspecific interactions of flavonoids with lipids can alter the membrane's features (e.g., thickness and fluctuations) as well as influence their therapeutic potentials. However, relatively little is known about the details of how flavonoids interact with lipid components. Structure-dependent interactions of a variety of flavonoids with phospholipid monolayers on a mercury (Hg) film electrode were established by rapid cyclic voltammetry (RCV). The data revealed that flavonoids adopting a planar configuration altered the membrane properties more significantly than nonplanar flavonoids. Quercetin, rutin, and tiliroside were selected for follow-up experiments with Langmuir monolayers, Brewster angle microscopy (BAM), and small-angle X-ray scattering (SAXS). Relaxation phenomena in DOPC monolayers and visualization of the surface with BAM revealed a pronounced monolayer stabilization effect with both quercetin and tiliroside, whereas rutin disrupted the monolayer structure rendering the surface entirely smooth. SAXS showed a monotonous membrane thinning for all compounds studied associated with an increase in the mean fluctuations of the membrane. Rutin, quercetin, and tiliroside decreased the bilayer thickness of DOPC by ∼0.45, 0.8, and 1.1 Šat 6 mol %, respectively. In addition to the novelty of using lipid monolayers to systematically characterize the structure-activity relationship (SAR) of a variety of flavonoids, this is the first report investigating the effect of tiliroside with biomimetic membrane models. All the flavonoids studied are believed to be localized in the lipid/water interface region. Both this localization and the membrane perturbations have implications for their therapeutic activity.