Search Results (9)

The term extracellular vesicles (EVs) includes a variety of anucleated, non-self-replicative particles released by cells, whose cargo content is compartmentalized by a lipidic bilayer membrane and includes proteins, DNA, and RNA (both coding and non-coding) molecules. MicroRNAs (miRs) are small non-coding RNA involved in gene expression regulation that functionally participate in inter-cellular communication as EV cargo. Natural Killer (NK) cells are innate immunity lymphocytes specialized in the killing of cancer cells and virally infected cells. Increasing evidence shows that NK cell-derived EVs contribute to the anti-tumoral activity of NK cells and that such effects are, at least in part, mediated by the miR cargo of these EVs. Conversely, cancer cells release EVs whose cargo includes proteins and miRs that impair NK cell function. These interactions highlight a central role for EV miRs both in the NK-mediated cytotoxicity and as a major immune-escape mechanism for cancer cells, ultimately contributing to the overall success or failure of NK cells in eliciting their anti-tumoral activity. Full article

Cellular membranes are essential for compartmentalization, maintenance of permeability, and fluidity in all three domains of life. Archaea belong to the third domain of life and have a distinct phospholipid composition. Membrane lipids of archaea are ether-linked molecules, specifically bilayer-forming dialkyl glycerol diethers (DGDs) and monolayer-forming glycerol dialkyl glycerol tetraethers (GDGTs). The antifungal allylamine terbinafine has been proposed as an inhibitor of GDGT biosynthesis in archaea based on radiolabel incorporation studies. The exact target(s) and mechanism of action of terbinafine in archaea remain elusive. Sulfolobus acidocaldarius is a strictly aerobic crenarchaeon thriving in a thermoacidophilic environment, and its membrane is dominated by GDGTs. Here, we comprehensively analyzed the lipidome and transcriptome of S. acidocaldarius in the presence of terbinafine. Depletion of GDGTs and the accompanying accumulation of DGDs upon treatment with terbinafine were growth phase-dependent. Additionally, a major shift in the saturation of caldariellaquinones was observed, which resulted in the accumulation of unsaturated molecules. Transcriptomic data indicated that terbinafine has a multitude of effects, including significant differential expression of genes in the respiratory complex, motility, cell envelope, fatty acid metabolism, and GDGT cyclization. Combined, these findings suggest that the response of S. acidocaldarius to terbinafine inhibition involves respiratory stress and the differential expression of genes involved in isoprenoid biosynthesis and saturation. Full article

Lipid membranes are a key component of living systems and have been essential to the origin of life. One hypothesis for the origin of life assumes the existence of protomembranes with ancient lipids formed by Fischer–Tropsch synthesis. We determined the mesophase structure and fluidity of a prototypical decanoic (capric) acid-based system, a fatty acid with a chain length of 10 carbons, and a lipid system consisting of a 1:1 mixture of capric acid with a fatty alcohol of equal chain length (C10 mix). To shed light on the mesophase behavior and fluidity of these prebiotic model membranes, we employed Laurdan fluorescence spectroscopy, which reports on the lipid packing and fluidity of membranes, supplemented by small-angle neutron diffraction data. The data are compared with data of the corresponding phospholipid bilayer systems of the same chain length, 1,2-didecanoyl-sn-glycero-3-phosphocholine (DLPC). We demonstrate that the prebiotic model membranes capric acid and the C10 mix show formation of stable vesicular structures needed for cellular compartmentalization at low temperatures only, typically below 20 °C. They reveal the fluid-like lipid dynamic properties needed for optimal physiological function. High temperatures lead to the destabilization of the lipid vesicles and the formation of micellar structures. Full article

Nanoscale lipid bilayers, or nanoliposomes, are generally spherical vesicles formed by the dispersion of phospholipid molecules in a water-based medium by energy input. The other nanoscale object discussed in this entry, i.e., tocosome, is a recently introduced bioactive carrier made mainly from tocopheryl phosphates. Due to their bi-compartmental structure, which consists of lipidic and aqueous compartments, these nanocarriers are capable of carrying hydrophilic and hydrophobic material separately or simultaneously. Nanoliposomes and tocosomes are able to provide protection and release of sensitive food-grade bioactive materials in a sustained manner. They are being utilized for the encapsulation of different types of bioactive materials (such as drugs, vaccines, antimicrobials, antioxidants, minerals and preservatives), for the enrichment and fortification of different food and nutraceutical formulations and manufacturing of functional products. However, a number of issues unique to the nutraceutical and food industry must first be resolved before these applications can completely become a reality. Considering the potentials and promises of these colloidal carrier systems, the present article reviews various aspects of nanoliposomes, in comparison with tocosomes, including the ingredients used in their manufacture, formation mechanisms and issues pertaining to their application in the formulation of health promoting dietary supplements and functional food products. Full article

Biological membranes are key elements for the maintenance of cell architecture and physiology. Beyond a pure barrier separating the inner space of the cell from the outer, the plasma membrane is a scaffold and player in cell-to-cell communication and the initiation of intracellular signals among other functions. Critical to this function is the plasma membrane compartmentalization in lipid microdomains that control the localization and productive interactions of proteins involved in cell signal propagation. In addition, cells are divided into compartments limited by other membranes whose integrity and homeostasis are finely controlled, and which determine the identity and function of the different organelles. Here, we review current knowledge on membrane lipid composition in the plasma membrane and endomembrane compartments, emphasizing its role in sustaining organelle structure and function. The correct composition and structure of cell membranes define key pathophysiological aspects of cells. Therefore, we explore the therapeutic potential of manipulating membrane lipid composition with approaches like membrane lipid therapy, aiming to normalize cell functions through the modification of membrane lipid bilayers. Full article

Polyphilic self-assembly leads to compartmentalization of space and development of complex structures in soft matter on different length scales, reaching from the morphologies of block copolymers to the liquid crystalline (LC) phases of small molecules. Whereas block copolymers are known to form membranes and interact with phospholipid bilayers, liquid crystals have been less investigated in this respect. Here, series of bolapolyphilic X-shaped molecules were synthesized and investigated with respect to the effect of molecular structural parameters on the formation of LC phases (part 1), and on domain formation in phospholipid bilayer membranes (part 2). The investigated bolapolyphiles are based on a rod-like π-conjugated oligo(phenylene ethynylene) (OPE) core with two glycerol groups being either directly attached or separated by additional ethylene oxide (EO) units to both ends. The X-shape is provided by two lateral alkyl chains attached at opposite sides of the OPE core, being either linear, branched, or semiperfluorinated. In this report, the focus is on the transition from polyphilic (triphilic or tetraphilic) to binary amphiphilic self-assembly. Polyphilic self-assembly, i.e., segregation of all three or four incorporated units into separate nano-compartments, leads to the formation of hexagonal columnar LC phases, representing triangular honeycombs. A continuous transition from the well-defined triangular honeycomb structures to simple hexagonal columnar phases, dominated by the arrangement of polar columns on a hexagonal lattice in a mixed continuum formed by the lipophilic chains and the OPE rods, i.e., to amphiphilic self-assembly, was observed by reducing the length and volume of the lateral alkyl chains. A similar transition was found upon increasing the length of the EO units involved in the polar groups. If the lateral alkyl chains are enlarged or replaced by semiperfluorinated chains, then the segregation of lateral chains and rod-like cores is retained, even for enlarged polar groups, i.e., the transition from polyphilic to amphiphilic self-assembly is suppressed. Full article

The plasma membrane is a highly compartmentalized, dynamic material and this organization is essential for a wide variety of cellular processes. Nanoscale domains allow proteins to organize for cell signaling, endo- and exocytosis, and other essential processes. Even in the absence of proteins, lipids have the ability to organize into domains as a result of a variety of chemical and physical interactions. One feature of membranes that affects lipid domain formation is membrane curvature. To directly test the role of curvature in lipid sorting, we measured the accumulation of two similar lipids, 1,2-Dihexadecanoyl-sn-glycero-3-phosphoethanolamine (DHPE) and hexadecanoic acid (HDA), using a supported lipid bilayer that was assembled over a nanopatterned surface to obtain regions of membrane curvature. Both lipids studied contain 16 carbon, saturated tails and a head group tag for fluorescence microscopy measurements. The accumulation of lipids at curvatures ranging from 28 nm to 55 nm radii was measured and fluorescein labeled DHPE accumulated more than fluorescein labeled HDA at regions of membrane curvature. We then tested whether single biotinylated DHPE molecules sense curvature using single particle tracking methods. Similar to groups of fluorescein labeled DHPE accumulating at curvature, the dynamics of single molecules of biotinylated DHPE was also affected by membrane curvature and highly confined motion was observed. Full article

The influence of cholesterol concentration on the formation of buckling structures is studied in a physisorbed polymer-tethered lipid monolayer system using epifluorescence microscopy (EPI) and atomic force microscopy (AFM). The monolayer system, built using the Langmuir-Blodgett (LB) technique, consists of 3 mol % poly(ethylene glycol) (PEG) lipopolymers and various concentrations of the phospholipid, 1-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine (SOPC), and cholesterol (CHOL). In the absence of CHOL, AFM micrographs show only occasional buckling structures, which is caused by the presence of the lipopolymers in the monolayer. In contrast, a gradual increase of CHOL concentration in the range of 0–40 mol % leads to fascinating film stress relaxation phenomena in the form of enhanced membrane buckling. Buckling structures are moderately deficient in CHOL, but do not cause any notable phospholipid-lipopolymer phase separation. Our experiments demonstrate that membrane buckling in physisorbed polymer-tethered membranes can be controlled through CHOL-mediated adjustment of membrane elastic properties. They further show that CHOL may have a notable impact on molecular confinement in the presence of crowding agents, such as lipopolymers. Our results are significant, because they offer an intriguing prospective on the role of CHOL on the material properties in complex membrane architecture. Full article

Recent developments in studies concerning cell-sized vesicles, such as liposomes with a lipid bilayer and water-in-oil droplets covered by a lipid monolayer, aim to realize the real-world modeling of living cells. Compartmentalization with a membrane boundary is essential for the organization of living systems. Due to the relatively large surface/volume ratio in microconfinement, the membrane interface influences phenomena related to biological functions. In this article, we mainly focus on the following subjects: (i) conformational transition of biopolymers in a confined space; (ii) molecular association on the membrane surface; and (iii) remote control of cell-sized membrane morphology. Full article