Lipid Tails Modulate Antimicrobial Peptide Membrane Incorporation and Activity

Antimicrobial peptides (AMPs) are cationic, amphipathic peptides that interact directly with lipid bilayers. AMPs generally interact with anionic lipid head groups, but it is less clear how the lipid tail length and saturation modulates interactions with membranes. Here, we used native mass spectrometry to measure the stoichiometry of three different AMPs-LL-37, indolicidin, and magainin-2-in lipid nanodiscs. We also measured the activity of these AMPs in large unilamellar vesicle leakage assays. We found that LL-37 formed specific hexamer complexes but with different assembly pathways and affinities that depended on the bilayer thickness. LL-37 was also most active in lipid bilayers containing longer, unsaturated lipids. In contrast, indolicidin incorporated to a higher degree into more fluid lipid bilayers but was more active with thinner, less fluid bilayers. Finally, magainin-2 incorporated to a higher degree into longer, unsaturated bilayers and showed more activity in these same conditions. Together, these data show that higher amounts of peptide incorporation generally led to higher activity and that AMPs tend to incorporate more into longer unsaturated lipid bilayers. However, the activity of AMPs was not always directly related to amount of peptide incorporated.

Ethosomes for Dermal Administration of Natural Active Molecules

: Ethosomes are nanovesicular carriers for dermal administration. Phospholipids, ethanol at relatively high concentrations (up to 50%) and water are their main components. Ethosomes are what we call “soft vesicles” with fluid bilayers due to the presence of ethanol. The composition and structure of the vesicles augment their ability to entrap molecules with various physicochemical properties and deliver them to the deep strata of skin. Since their first design, ethosomal systems have been extensively investigated for a wide range of applications. : This review focuses on work carried out in vitro, in vivo in animal models and in humans in clinical studies, with ethosomal formulations containing natural active molecules for the treatment of skin disorders. Skin bacterial and fungal infections, skin inflammation, acne vulgaris, arthritis, and skin cancer are examples of disorders managed successfully by ethosomal systems. Furthermore, Ethosomes loaded with a number of naturally occurring compounds for cosmetic applications are also reported. The efficient treatments together with a good safety profile and lack of toxicity or irritation paved the way towards the development of new dermal therapies.

Effect of alkan-1-ols on the structure of dopc model membrane

The effect of general anaesthetics alkan-1-ols (CnOH, where n = 10, 12, 14, 16 and 18 is the number of carbon atoms in the molecule) on the structure of dioleoylphosphatidylcholine (DOPC) model membrane was studied by small-angle neutron scattering (SANS) and small-angle neutron diffraction (SAND). Fluid bilayers were prepared at CnOH:DOPC = 0.3 molar ratio. The results of both the experiments show that bilayer thickness - a thickness parameter dg in the case of SANS and lamellar repeat distance D in the case of SAND - increases with increasing n. A coexistence of two lamellar phases with different D was detected by measuring the C18OH+DOPC oriented sample.

Influence of isoform-specific Ras lipidation motifs on protein partitioning and dynamics in model membrane systems of various complexity

The partitioning of the lipidated signaling proteins N-Ras and K-Ras4B into various membrane systems, ranging from single-component fluid bilayers, binary fluid mixtures, heterogeneous raft model membranes up to complex native-like lipid mixtures (GPMVs) in the absence and presence of integral membrane proteins have been explored in the last decade in a combined chemical-biological and biophysical approach. These studies have revealed pronounced isoform-specific differences regarding the lateral distribution in membranes and formation of protein-rich membrane domains. In this context, we will also discuss the effects of lipid head group structure and charge density on the partitioning behavior of the lipoproteins. Moreover, the dynamic properties of N-Ras and K-Ras4B have been studied in different model membrane systems and native-like crowded milieus. Addition of crowding agents such as Ficoll and its monomeric unit, sucrose, gradually favors clustering of Ras proteins in forming small oligomers in the bulk; only at very high crowder concentrations association is disfavored.

Remodeling of membrane compartments: some consequences of membrane fluidity

Biological membranes consist of fluid bilayers with many lipid and protein components. This fluidity implies a high flexibility that allows the membranes to attain a large variety of different shapes. One important shape parameter is the spontaneous curvature, which describes the asymmetry between the two leaflets of a bilayer and can be changed by adsorption of ‘particles’ such as ions or proteins from the aqueous phases. Membrane fluidity also implies that the membranes can change their local composition via lateral diffusion and form intramembrane compartments. Two mechanisms for the formation of such compartments can be distinguished: membrane segmentation arising from structured environments and domain formation as a result of phase separation within the membranes. The interplay between these two mechanisms provides a simple and generic explanation for the difficulty to observe phase domains in vivo. Intramembrane domains can form new membrane compartments via budding and tubulation processes. Which of these two processes actually occurs depends on the fluid-elastic properties of the domains, on the adsorption kinetics, and on external constraints arising, e.g., from the osmotic conditions. Vesicles are predicted to unbind from adhesive surfaces via tubulation when the spontaneous curvature of their membranes exceeds a certain threshold value.