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 Å at 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

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

Nature's Swiss Army Knives: Ovipositor Structure Mirrors Ecology in a Multitrophic Fig Wasp Community

Resource partitioning is facilitated by adaptations along niche dimensions that range from morphology to behaviour. The exploitation of hidden resources may require specially adapted morphological or sensory tools for resource location and utilisation. Differences in tool diversity and complexity can determine not only how many species can utilize these hidden resources but also how they do so.The sclerotisation, gross morphology and ultrastructure of the ovipositors of a seven-member community of parasitic wasps comprising of gallers and parasitoids developing within the globular syconia (closed inflorescences) of Ficus racemosa (Moraceae) was investigated. These wasps also differ in their parasitism mode (external versus internal oviposition) and their timing of oviposition into the expanding syconium during its development. The number and diversity of sensilla, as well as ovipositor teeth, increased from internally ovipositing to externally ovipositing species and from gallers to parasitoids. The extent of sclerotisation of the ovipositor tip matched the force required to penetrate the syconium at the time of oviposition of each species. The internally ovipositing pollinator had only one type of sensillum and a single notch on the ovipositor tip. Externally ovipositing species had multiple sensilla types and teeth on their ovipositors. Chemosensilla were most concentrated at ovipositor tips while mechanoreceptors were more widely distributed, facilitating the precise location of hidden hosts in these wasps which lack larval host-seeking behaviour. Ovipositor traits of one parasitoid differed from those of its syntopic galler congeners and clustered with those of parasitoids within a different wasp subfamily. Thus ovipositor tools can show lability based on adaptive necessity, and are not constrained by phylogeny.Ovipositor structure mirrored the increasingly complex trophic ecology and requirements for host accessibility in this parasite community. Ovipositor structure could be a useful surrogate for predicting the biology of parasites in other communities

Substituents modulate biphenyl penetration into lipid membranes

Electrochemical impedance techniques and fluorescence spectroscopic methods have been applied to the study of the interaction of ortho (o)-, meta (m)- and para (p)-Cl-, o-, m- and p-HO-, p-H3CO-, p-H3C-, p-NC- and p-O3− S- substituted biphenyls (BPs) with Hg supported dioleoyl phosphatidylcholine (DOPC) monolayers and DOPC vesicles. Non-planar o-substituted BPs exhibit the weakest interactions whereas planar p-substituted BPs interact to the greatest extent with the DOPC layers. The substituted BP/DOPC monolayer and bilayer interaction depends on the effect of the substituent on the aromatic electron density, which is related to the substituents’ mesomeric Hammetts constants. Substituted BPs with increased ring electron density do not increase the DOPC monolayer thickness on Hg and penetrate the DOPC vesicle membranes to the greatest extent. Substituted BPs with lower ring electron density can cause an increase in the monolayer’s thickness on Hg depending on their location and they remain in the interfacial and superficial layer of the free standing DOPC membranes. Quantum mechanical calculations correlate the binding energy between the substituted BP rings and methyl acetate, as a model for the –CH2-(CO)O-CH2- fragment of a DOPC molecule, with the location of BPs within the DOPC monolayer

Interactions of flavonoids with lipidic mesophases

Along having various health benefits, flavonoids are increasingly being recognized as potent antioxidants and anticancer compounds. However, despite significant efforts over the last few decades to develop novel delivery systems providing higher drug bioavailability, many biofunctional aspects are still unsolved. In this chapter, we review the current knowledge on flavonoid–lipid interactions and elucidate in particular their influence on lipidic self-assembled mesophases. The interactions of flavonoids with phospholipid-based planar membranes and monoglycerides-based curved membranes are presented in detail; the main structural changes in these self-assemblies are summarized, and the correlation between membranes’ structure and function is discussed. Based on those considerations, especially the importance of membrane curvature and possible biological implications are highlighted

Interactions of flavonoids with lipidic mesophases

Along having various health benefits, flavonoids are increasingly being recognized as potent antioxidants and anticancer compounds. However, despite significant efforts over the last few decades to develop novel delivery systems providing higher drug bioavailability, many biofunctional aspects are still unsolved. In this chapter, we review the current knowledge on flavonoid–lipid interactions and elucidate in particular their influence on lipidic self-assembled mesophases. The interactions of flavonoids with phospholipid-based planar membranes and monoglycerides-based curved membranes are presented in detail; the main structural changes in these self-assemblies are summarized, and the correlation between membranes’ structure and function is discussed. Based on those considerations, especially the importance of membrane curvature and possible biological implications are highlighted

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