Chemistry and Physics of Lipids最新文献

The use of dendrimers as nanovectors for nucleic acids or drugs requires the understanding of their interaction with biological membranes. This study investigates the impact of 1st generation polyphenolic carbosilane dendrimers on biological and model lipid membranes using several biophysical methods. While the increase in the z-average size of DMPC/DPPG liposomes correlated with the number of caffeic acid residues included in the dendrimer structure, dendrimers that contained polyethylene glycol chains generated lower zeta potential when interacting with a liposomal membrane. The increase in the fluorescence anisotropy of DPH and TMA-DPH probes incorporated into erythrocyte membranes predicted the ability of dendrimers to affect membrane fluidity in the hydrophobic interior and hydrophilic/polar region of a lipid bilayer. The presence of caffeic acid and polyethylene glycol chains in the dendrimer structure affected the thermodynamical properties of the membrane lipid matrix.

The stratum corneum (SC) presents certain limitations for topical administration of medication, which can be overcome using penetration enhancers (PEs) such as terpene (TP). The SC is also crucial for maintaining the skin barrier and consists of two lamellar structures: the short periodicity phase (SPP) and long periodicity phase (LPP). In this study, we monitored changes in the X-ray diffraction peaks of the human SC, 30 min after TP application (neroridol, 1,8-cineol, and d-limonene). With the application of nerolidol, no significant changes were observed in the small-angle diffraction peak positions for the lamellar structure of SPP, but the integrated intensity decreased. On the contrary, when applying 1,8-cineole and d-limonene, a lower angle peak shift with broadening of the peak width of SPP diffraction peaks was observed for d-limonene than for 1,8-cineole, and the degree of peak shift and width broadening was greater for d-limonene than for 1,8-cineole. The diffraction peaks of LPP disappeared when 1,8-cineole and d-limonene were applied. These results indicate that the degree of interaction between the SC and TP differs depending on the molecular species, and d-limonene and 1,8-cineole exhibit penetration-enhancing via lamellar structure disruption of both SPP and LPP, immediately after application.

Melting of brain sphingomyelin (bSM) manifests as a broad feature in the DSC curve that encompasses the temperature range of 25 – 45 °C, with two distinguished maxima originating from the phase transitions of two the most abundant components: C24:1 (T_m,1) and C18:0 (T_m,2). While C24:1/C18:0 sphingomyelin transforms from the gel/ripple phase to the fluid/fluid phase, the dynamics of water molecules in the interfacial layer remain completely unknown. Therefore, we carried out a calorimetric (DSC), spectroscopic (temperature-dependent UV-Vis and fluorescence) and MD simulation study of bSM in the absence/presence of Laurdan® (bSM ± L) suspended in Britton-Robinson buffer with three different pH values, 4 (BRB4), 7 (BRB7) and 9 (BRB9), and of comparable ionic strength (I = 100 mM). According to DSC, $\bar{T}$_{m, 1} (≈ 34.5 °C/≈ 32.1 °C) and $\bar{T}$_{m, 2} (≈ 38.0 °C/≈ 37.2 °C) of bSM suspended in BRB4, BRB7, and BRB9 in the absence/presence of Laurdan® are found to be practically pH-independent. Turbidity-based data (UV-Vis) detected both qualitative and quantitative differences in the response of bSM suspended in BRB4/BRB7/BRB9 ($\bar{T}$_m: ∼ 35 °C/32.0 ± 0.2 °C/36.4 ± 0.4), suggesting an intricate interplay of weakening of van der Waals forces between their hydrocarbon chains and of increased hydration in the polar headgroups region during melting. The temperature-dependent response of Laurdan® reported a discontinuous, pH-dependent change in the reorientation of interfacial water molecules that coincides with the melting of C24:1 lipids (on average, $\bar{T}$_{m (LTC/HTC)}: ≈ 31.8 °C/30.6 °C/30.5 °C). MD simulations elucidated the impact of Laurdan® on a change in the physicochemical properties of bSM lipids and characterized the hydrogen bond network at the interface at 20 °C and 50 °C.

Nanodiscs are discoidal lipoproteins that have often been used as vehicles to study membrane proteins in their native configuration. Nanodiscs have been primarily made from synthetic lipids. However, nanodiscs also offer a format by which native lipids can be studied in their natural configuration. Here, we present a method to synthesize nanodiscs from bacterial total lipid extracts using the biothreat agent, Yersinia pestis, as a proof-of-concept. The creation of nanoparticles entirely composed of bacterial lipids supports membrane characterization and vaccine antigen discovery without the inherent safety concerns associated with live bacterial cells of this Tier 1 select agent pathogen.

Staphylococcus aureus infections and its biofilm removal is an important concern in health care management. Methicillin-resistant S. aureus is responsible for severe morbidity and mortality worldwide. The extensive use of disinfectants against biofilms has led to negative environmental impacts. Developing new and more potent biofilm eradication agents with minimal detrimental effects on human and environmental health is currently on the agenda. The alkyl esters of L-ascorbic acid (ASCn) are antioxidant amphiphiles, which show antimicrobial capacity against methicillin-sensitive and resistant S. aureus strains. ASC12 and ASC14 formulations are able to kill the persister cells of the deepest layers of the biofilm. We tested the hypothesis that the antimicrobial and antibiofilm capacity found for the ASCn emerges from a combined effect of its amphiphilic and their redox capacity. This mechanism appears related to: I) a larger diffusion capacity of the ASC12 micelles than ASC14 and ASC16 microstructures; II) the neutralization of the ASCn acid hydroxyl when the amphiphile reaches the surface of an anionic surface, followed by a rapid insertion; III) the disruption of cell membrane by alteration of membrane tension and structure and IV) ASCn accumulation in the cell membrane or biofilm extracellular matrix surfaces, reducing functional chemical groups and affecting its biological function.

Phosphatidylserine (PtdS) is classified as a glycerophospholipid and a primary anionic phospholipid and is particularly abundant in the inner leaflet of the plasma membrane in neural tissues. It is synthesized from phosphatidylcholine or phosphatidylethanolamine by exchanging the base head group with serine, and this reaction is catalyzed by PtdS synthase-1 and PtdS synthase-2 located in the endoplasmic reticulum. PtdS exposure on the outside surface of the cell is essential for eliminating apoptotic cells and initiating the blood clotting cascade. It is also a precursor of phosphatidylethanolamine, produced by PtdS decarboxylase in bacteria, yeast, and mammalian cells. Furthermore, PtdS acts as a cofactor for several necessary enzymes that participate in signaling pathways. Beyond these functions, several studies indicate that PtdS plays a role in various cerebral functions, including activating membrane signaling pathways, neuroinflammation, neurotransmission, and synaptic refinement associated with the central nervous system (CNS). This review discusses the occurrence of PtdS in nature and biosynthesis via enzymes and genes in plants, yeast, prokaryotes, mammalian cells, and the brain, and enzymatic synthesis through phospholipase D (PLD). Furthermore, we discuss metabolism, its role in the CNS, the fortification of foods, and supplementation for improving some memory functions, the results of which remain unclear. PtdS can be a potentially beneficial addition to foods for kids, seniors, athletes, and others, especially with the rising consumer trend favoring functional foods over conventional pills and capsules. Clinical studies have shown that PtdS is safe and well tolerated by patients.

As key mediators in a wide array of signaling events, phosphoinositides (PIPs) orchestrate the recruitment of proteins to specific cellular locations at precise moments. This intricate spatiotemporal regulation of protein activity often necessitates the localized enrichment of the corresponding PIP. We investigate the extent and thermal stabilities of phosphatidylinositol-4-phosphate (PI(4)P), phosphatidylinositol-4,5-bisphosphate (PI(4,5)P₂ and phosphatidylinositol-3,4,5-trisphosphate (PI(3,4,5)P₃) clusters with calcium and magnesium ions. We observe negligible or minimal clustering of all examined PIPs in the presence of Mg²⁺ ions. While PI(4)P shows in the presence of Ca²⁺ no clustering, PI(4,5)P₂ forms with Ca²⁺ strong clusters that exhibit stablity up to at least 80°C. The extent of cluster formation for the interaction of PI(3,4,5)P₃ with Ca²⁺ is less than what was observed for PI(4,5)P₂, yet we still observe some clustering up to 80°C. Given that cholesterol has been demonstrated to enhance PIP clustering, we examined whether bivalent cations and cholesterol synergistically promote PIP clustering. We found that the interaction of Mg²⁺ or Ca²⁺ with PI(4)P remains extraordinarily weak, even in the presence of cholesterol. In contrast, we observe synergistic interaction of cholesterol and Ca²⁺ with PI(4,5)P₂. Also, in the presence of cholesterol, the interaction of Mg²⁺ with PI(4,5)P₂ remains weak. PI(3,4,5)P₃ does not show strong clustering with cholesterol for the experimental conditions of our study and the interaction with Ca²⁺ and Mg²⁺ was not influenced by the presence of cholesterol.

This study explores the impact of the antimicrobial peptide magainin 2 (Mag2) on lipid bilayers with varying compositions. We employed high-resolution atomic force microscopy (AFM) to reveal a dynamic spectrum of structural changes induced by Mag2. Our AFM imaging unveiled distinct structural alterations in zwitterionic POPC bilayers upon Mag2 exposure, notably the formation of nanoscale depressions within the bilayer surface, which we term as "surface pores" to differentiate them from transmembrane pores. These surface pores are characterized by a limited depth that does not appear to fully traverse the bilayer and reach the opposing leaflet. Additionally, our AFM-based force spectroscopy investigation on POPC bilayers revealed a reduction in bilayer puncture force (F_P) and Young's modulus (E) upon Mag2 interaction, indicating a weakening of bilayer stability and increased flexibility, which may facilitate peptide insertion. The inclusion of anionic POPG into POPC bilayers elucidated its modulatory effects on Mag2 activity, highlighting the role of lipid composition in peptide-bilayer interactions. In contrast to surface pores, Mag2 treatment of E. coli total lipid extract bilayers resulted in increased surface roughness, which we describe as a fluctuation-like morphology. We speculate that the weaker cohesive interactions between heterogeneous lipids in E. coli bilayers may render them more susceptible to Mag2-induced perturbations. This could lead to widespread disruptions manifested as surface fluctuations throughout the bilayer, rather than the formation of well-defined pores. Together, our findings of nanoscale bilayer perturbations provide useful insights into the molecular mechanisms governing Mag2-membrane interactions.