Apolar Lipids Research Articles

Neutral lipids restrict the mobility of broken DNA molecules during comet assays.

One widespread technique to assess in relative terms the amount of broken DNA present in the genome of individual cells consists of immobilizing the cell's nucleus under an agarose pad (called the nucleoid) and subjecting the whole genome to electrophoresis to force broken DNA molecules out of it. Since the migrating broken DNA molecules create a tail behind the nucleoid, this technique is named the comet assay. While performing comet assays regularly, we systematically observed circular regions devoid of DNA within the nucleoid region. We characterize here that these correspond to clusters of neutral (apolar) lipids, since they could be labeled with neutral lipid-dying molecules, increased when cells were fed with oleic acid, and were irresponsive to the electrophoretic field. Of relevance, de-lipidation assays, either in vivo, or in vitro using acetone, show that these neutral lipids (NL) within the nucleoid limit the ability of broken DNA molecules to migrate into the comet tail. From a technical point of view, we show that de-lipidation permits a wider range for the detection of broken DNA molecules. Biologically, we put forward the notion that NL in contact with DNA may locally exert regulatory functions within the cell's nucleus.

The role of antibiotic-derived mycobacterial vesicles in tuberculosis pathogenesis

Pulmonary tuberculosis (TB) causes progressive and irreversible damage to lung tissue, a damage that may not fully resolve after treatment. Mycobacterial vesicles (MVs), which are poorly understood, may contribute to TB pathology. This study investigated the effects of stress, such as treatment with conventional TB antibiotics rifampicin, isoniazid, ethambutol, or treatment with an antimycobacterial peptide (NZX), on mycobacterial vesiculation. Stress from minimal inhibitory concentrations of antibiotics, or peptide all increased MV formation. Electron microscopy and lipid profiling revealed that these vesicles, about 40 nm in size, were released from the bacterial inner membrane and consisted of apolar lipids. Using mass spectrometry, the study identified key differences in MVs protein cargo dependent on the antibiotic used, especially with ethambutol-induced MVs that contained proteins from several mycobacterial pathways. Additionally, toxicology analysis using different concentrations of MVs on primary human macrophages and the monocytic cells indicated that MVs from the different treatments were not toxic to human cells, however induced specific inflammatory profiles. In conclusion, this study identified mycobacterial vesicles to be a potential contributor to tuberculosis pathology.

Targeted metabolomics reveals progression of early Alzheimer’s disease in TgF344 transgenic rats

AbstractBackgroundAlzheimer’s disease (AD) is an aging‐related neurodegenerative disease, leading to the progressive loss of memory and other cognitive functions. As there is still no cure for AD, the growth in the number of susceptible individuals represents a major emerging threat to public health. Current AD diagnosis methods can only identify patients in the advanced stage of the disease, that means when the dementia is already present. This highlights the need for new approaches for the diagnosis of AD at earlier stages, especially before the symptoms appear. In addition, AD is reported to be closely linked with abnormal lipid metabolism. The objective of this study is to identify blood‐based lipid biomarkers to gain a more comprehensive understanding of what causes AD and its subsequent development.MethodA longitudinal study with 4 different ages (12 weeks, 25 weeks, 50 weeks, and 85 weeks) was conducted in TgF344 transgenic (AD) and wild‐type (WT) rats. Metabolomics profiling of EDTA plasma yielded 811 metabolites after quality control. Metabolites profiled included medium and apolar lipids covering 27 lipid classes, signaling lipids including oxylipins, isoprostanes, eicosanoids, bile acids, endocannabinoids. All data was log2 transformed. All statistical analysis and visualizations were performed in R.ResultThe sphingomyelins (SM) were decreased at 25 weeks with AD having more SM expressed than the WT group, while this was reversed at 50 weeks. In 12 weeks, the volcano plot of AD/WT showed more significant lipids on female (p<0.05:15) than male (p<0.05:2). Whereas, in 25 weeks, male (p<0.05:56) showed more significant lipids than female (p<0.05:7). The ratios of an eicosanoid to its seven products were first decreased, then increased over time in both WT and AD group. However, the WT group reached its minimum at 50 weeks, while the AD group reached its minimum at 25 weeks. Sex differences were found in AD/WT among all ages.ConclusionLipidomics data on longitudinal course of potential lipid biomarkers in plasma of WT and AD rats show some effects of AD and/or aging. It is anticipated that this information will contribute to developing lipid biomarker fingerprints for diagnosis and monitoring AD progression distinct from normal aging.

Genetic Targeting of Solvatochromic Dyes for Probing Nanoscale Environments of Proteins in Organelles.

A variety of protein tags are available for genetically encoded protein labeling, which allow their precise localization and tracking inside the cells. A new dimension in protein imaging can be offered by combining protein tags with polarity-sensitive fluorescent probes, which provide information about local nanoscale environments of target proteins within the subcellular compartments (organelles). Here, we designed three fluorescent probes based on solvatochromic nile red dye, conjugated to a HaloTag reactive targeting group through polyethylene glycol linkers of varying lengths. The probe with medium linker length, NR12-Halo, was found to label specifically a large variety of proteins localized in defined cell compartments, such as plasma membranes (outer and inner leaflets), endoplasmic reticulum, Golgi apparatus, cytosol, microtubules, actin, and chromatin. Owing to its polarity-sensitive fluorophore, the probe clearly distinguished the proteins localized within apolar lipid membranes from other proteins. Moreover, it revealed dramatic changes in the environment during the life cycle of proteins from biosynthesis to their expected localization and, finally, to recycling inside lysosomes. Heterogeneity in the local polarity of some membrane proteins also suggested a formation of low-polar protein aggregates, for example, within cell-cell contacts. The approach also showed that mechanical stress (cell shrinking by osmotic shock) induced a general polarity decrease in membrane proteins, probably due to the condensation of biomolecules. Finally, the nanoenvironment of some membrane proteins was affected by a polyunsaturated fatty acid diet, which provided the bridge between organization of lipids and proteins. The developed solvatochromic HaloTag probe constitutes a promising tool for probing nanoscale environments of proteins and their interactions within subcellular structures.

The membrane regulator squalane increases membrane rigidity under high hydrostatic pressure in archaeal membrane mimics.

Apolar lipids within the membranes of archaea are thought to play a role in membrane regulation. In this work we explore the effect of the apolar lipid squalane on the dynamics of a model archaeal-like membrane, under pressure, using neutron spin echo spectroscopy. To the best of our knowledge, this is the first report on membrane dynamics at high pressure using NSE spectroscopy. Increasing pressure leads to an increase in membrane rigidity, in agreement with other techniques. The presence of squalane in the membrane results in a stiffer membrane supporting its role as a membrane regulator.

Advanced unified monophasic lipid extraction protocol with wide coverage on the polarity scale optimized for large-scale untargeted clinical lipidomics analysis of platelets

Lipid extraction is a critical step in sample preparation of lipidomics studies. Biphasic liquid-liquid extraction protocol with methyl tert-butyl ether (MTBE)/methanol (MeOH) as organic solvents are widely adopted by researchers nowadays as an eco-friendly replacement of classic Folch, and Bligh&Dyer protocols. Yet, it has some limitations such as suboptimal performance for the most polar lipids (e.g. acylcarnitines), complicated handling as it requires phase separation, and is therefore non-ideal for large-scale clinical studies. To advance the extraction protocol for large-scale clinical lipidomics, in this study we explored i) 6 different extraction solvent systems, ii) distinct processing procedures (sonication, mechanical cell lysis and bead homogenizer), and iii) also 7 different reconstitution solvents. The extraction systems investigated included biphasic systems MTBE/MeOH/H2O and Hexane/2-propanol (IPA)/1 M acetic acid, and monophasic systems MTBE/MeOH/CHCl3, IPA/H2O (90% IPA), MeOH/MTBE/IPA, and IPA/H2O/MTBE as solvent system for lipid extraction of human platelets. Extraction recovery was investigated by repeated extraction cycles. Subcellular extraction efficiency was assessed by the mitochondria-specific cardiolipins. It turned out that monophasic extraction with MeOH/MTBE/IPA (1.3:1:1, v/v/v), bead homogenizer for cell disruption and MeOH/MTBE (1:1, v/v) as reconstitution solvent provide optimal cellular and subcellular extraction efficiencies for both polar (e.g. acylcarnitines) and apolar lipids (e.g. triglycerides). It is simplified (no phase separation), eco-friendly (reduced solvent consumption and no halogenated ones), fast (5 min for 24 samples in parallel), and can be easily adapted for cells, plasma, and tissue. Therefore, it has great potential for large-scale clinical lipidomics studies.

Triglyceride Lenses at the Air-Water Interface as a Model System for Studying the Initial Stage in the Biogenesis of Lipid Droplets.

Lipid droplets (LD) are intracellular structures consisting of an apolar lipid core, composed mainly of triglycerides (TG) and steryl esters, coated by a lipid-protein mixed monolayer. The mechanisms underlying LD biogenesis at the endoplasmic reticulum membrane are a matter of many current investigations. Although models explaining the budding-off of protuberances of phase-segregated TG inside bilayers have been proposed recently, the assumption of such initial blisters needs further empirical support. Here, we study mixtures of egg phosphatidylcholine (EPC) and TG at the air-water interface in order to describe some physical properties and topographic stability of TG bulk structures in contact with interfaces. Brewster angle microscopy images revealed the appearance of microscopic collapsed structures (CS) with highly reproducible lateral size (∼1 μm lateral radius) not varying with lateral packing changes and being highly stable at surface pressures (π) beyond collapse. By surface spectral fluorescence microscopy, we were able to characterize the solvatochromism of Nile Red both in monolayers and inside CS. This allowed to conclude that CS corresponded to a phase of liquid TG and to characterize them as lenses forming a three-phase (oil-water-air) system. Thereby, the thicknesses of the lenses could be determined, observing that they were dramatically flattened when EPC was present (6-12 nm compared to 30-50 nm for lenses on EPC/TG and TG films, respectively). Considering the shape of lenses, the interfacial tensions, and the Neumann's triangle, this experimental approach allows one to estimate the oil-water interfacial tension acting at each individual microscopic lens and at varying compression states of the surrounding monolayer. Thus, lenses formed on air-water Langmuir films can serve to assess variables of relevance to the initial step of LD biogenesis, such as the degree of dispersion of excluded-TG phase and shape, spatial distribution, and oil-water interfacial tension of lenses.

Apolar Polyisoprenoids Located in the Midplane of the Bilayer Regulate the Response of an Archaeal-Like Membrane to High Temperature and Pressure.

Archaea are known to inhabit some of the most extreme environments on Earth. The ability of archaea possessing membrane bilayers to adapt to high temperature (>85°C) and high pressure (>1,000 bar) environments is proposed to be due to the presence of apolar polyisoprenoids at the midplane of the bilayer. In this work, we study the response of this novel membrane architecture to both high temperature and high hydrostatic pressure using neutron diffraction. A mixture of two diether, phytanyl chain lipids (DoPhPC and DoPhPE) and squalane was used to model this novel architecture. Diffraction data indicate that at high temperatures a stable coexistence of fluid lamellar phases exists within the membrane and that stable coexistence of these phases is also possible at high pressure. Increasing the amount of squalane in the membrane regulates the phase separation with respect to both temperature and pressure, and also leads to an increase in the lamellar repeat spacing. The ability of squalane to regulate the ultrastructure of an archaea-like membrane at high pressure and temperature supports the hypothesis that archaea can use apolar lipids as an adaptive mechanism to extreme conditions.

Influence of earthworms on apolar lipid features in soils after 1 year of incubation

Molecular and compound specific isotope compositions of apolar lipids were characterized in soil mesocosms incubated for 1 year with or without 13C-labelled plant residues and earthworms, in order to investigate, at the molecular scale, the effect of earthworms on the fate of organic matter (OM) in soils. Molecular and isotope composition of long chain alkanes in casts confirmed that earthworms preferentially ingest soil fractions rich in plant debris. Apolar lipid specific isotope composition allowed calculation of the proportion of carbon derived from the labelled residues (Clab). Casts displayed higher Clab values than surrounding soil while soil without earthworm exhibited intermediate Clab. The odd-over-even predominance (OEP) of alkanes suggested they are probably less degraded in casts than in the surrounding soil. Taken together, OEP and Clab values suggested that besides high incorporation of plant residues, earthworms may also favor the preservation of plant apolar lipids in their casts. Additionally, chain length and isotope pattern of alkanes further suggested root lipids were probably less degraded than shoot lipids. High 13C-incorporation level for the bacterial biomarker hopene provided evidence for intense recycling of plant OM and suggested further contribution of bacterial necromass to soil OM.

Crustacean Hemolymph Lipoproteins.

Lipoproteins mediate the transport of apolar lipids in the hydrophilic environment of physiological fluids such as the vertebrate blood and the arthropod hemolymph. In this overview, we will focus on the hemolymph lipoproteins in Crustacea that have received most attention during the last years: the high density lipoprotein/β-glucan binding proteins (HDL-BGBPs), the vitellogenins (VGs), the clotting proteins (CPs) and the more recently discovered large discoidal lipoproteins (dLPs). VGs are female specific lipoproteins which supply both proteins and lipids as storage material for the oocyte for later use by the developing embryo. Unusual within the invertebrates, the crustacean yolk proteins-formerly designated VGs-are more related to the ApoB type lipoproteins of vertebrates and are now termed apolipocrustaceins. The CPs on the other hand, which are present in both sexes, are related to the (sex specific) VGs of insects and vertebrates. CPs serve in hemostasis and wound closure but also as storage proteins in the oocyte. The HDL-BGBPs are the main lipid transporters, but are also involved in immune defense. Most crustacean lipoproteins belong to the family of the large lipid transfer proteins (LLTPs) such as the intracellular microsomal triglyceride transfer protein, the VGs, CPs and the dLPs. In contrast, the HDL-BGBPs do not belong to the LLTPs and their relationship with other lipoproteins is unknown. However, they originate from a common precursor with the dLPs, whose functions are as yet unknown. The majority of lipoprotein studies have focused on decapod crustaceans, especially shrimps, due to their economic importance. However, we will present evidence that the HDL-BGBPs are restricted to the decapod crustaceans which raises the question as to the main lipid transporting proteins of the other crustacean groups. The diversity of crustaceans lipoproteins thus appears to be more complex than reflected by the present state of knowledge.

Induction of non-lamellar phases in archaeal lipids at high temperature and high hydrostatic pressure by apolar polyisoprenoids

It is now well established that cell membranes are much more than a barrier that separate the cytoplasm from the outside world. Regarding membrane's lipids and their self-assembling, the system is highly complex, for example, the cell membrane needs to adopt different curvatures to be functional. This is possible thanks to the presence of non-lamellar-forming lipids, which tend to curve the membrane. Here, we present the effect of squalane, an apolar isoprenoid molecule, on an archaea-like lipid membrane. The presence of this molecule provokes negative membrane curvature and forces lipids to self-assemble under inverted cubic and inverted hexagonal phases. Such non-lamellar phases are highly stable under a broad range of external extreme conditions, e.g. temperatures and high hydrostatic pressures, confirming that such apolar lipids could be included in the architecture of membranes arising from cells living under extreme environments.

Sweep Jet Collection Laser-Induced Acoustic Desorption Atmospheric Pressure Photoionization for Lipid Analysis Applications.

Laser-induced acoustic desorption coupled to microplasma-based atmospheric pressure photoionization (LIAD-APPI) using a nebulized sweep jet to aid in dopant introduction and ion transmission has been applied to the analysis of model, apolar lipid compounds. Specifically, several sterols, sterol esters, and triacylglycerols were detected using dopants such as anisole and toluene. Additionally, several triacylglycerols, sterols, carboxylic acids, and hopanoids were detected from complex mixtures of olive oil and Australian shale rock extract as a first demonstration of the applicability of LIAD-APPI on real-world samples. Detection limits using a sweep jet configuration for α-tocopherol and cholesterol were found to be 609 ± 61 and 292 ± 29fmol, respectively. For sterol esters and triacylglycerols with a large number of double bonds in the fatty acid chain, LIAD-APPI was shown to yield greater molecular ion or [M+NH4]+ abundances than those with saturated fatty acid chains. Dopants such as anisole and toluene, with ionization potentials (IPs) of 8.2 and 8.8eV, respectively, were tested. A greater degree of fragmentation with several of the more labile test compounds was observed using toluene. Overall, LIAD-APPI with a nebulized sweep jet requires minimal sample preparation and is a generally useful and sensitive analysis technique for low-polarity mixtures of relevance to biochemical assays and geochemical profiling. Graphical Abstract.

Estimation of anthropogenic organo-chlorine, bromine and iodine compounds in apolar lipid fractions of bovine milk by solid-phase extraction and neutron activation analysis (SPE–NAA)

Milk lipids were separated using a hexane:isopropanol mixture; then they were fractionated into apolar, medium polar and polar portions by SPE using a LC-Si column. The apolar fraction was further separated into 4 more portions depending on their polarity by another SPE method using a Florosil column. Levels of Cl, Br and I were measured by NAA. Halogens were detected in all separated fractions; but their highest levels were found in the most apolar fraction containing hydrocarbons which strongly indicates the presence of anthropogenic organohalogen compounds in milk. In addition, iodide and iodate ions in whole milk samples were measured.

One- vs two-phase extraction: re-evaluation of sample preparation procedures for untargeted lipidomics in plasma samples

Lipidomics is a rapidly developing field in modern biomedical research. While LC-MS systems are able to detect most of the known lipid classes in a biological matrix, there is no single technique able to extract all of them simultaneously. In comparison with two-phase extractions, one-phase extraction systems are of particular interest, since they decrease the complexity of the experimental procedure. By using an untargeted lipidomics approach, we explored the differences/similarities between the most commonly used two-phase extraction systems (Folch, Bligh and Dyer, and MTBE) and one of the more recently introduced one-phase extraction systems for lipid analysis based on the MMC solvent mixture (MeOH/MTBE/CHCl3). The four extraction methods were evaluated and thoroughly compared against a pooled extract that qualitatively and quantitatively represents the average of the combined extractions. Our results show that the lipid profile obtained with the MMC system displayed the highest similarity to the pooled extract, indicating that it was most representative of the lipidome in the original sample. Furthermore, it showed better extraction efficiencies for moderate and highly apolar lipid species in comparison with the Folch, Bligh and Dyer, and MTBE extraction systems. Finally, the technical simplicity of the MMC procedure makes this solvent system highly suitable for automated, untargeted lipidomics analysis.

Assessment of apolar lipids in subseafloor rocks and potential contaminants from the Atlantis Massif (IODP Expedition 357)

International Ocean Discovery Program Expedition 357 drilled 17 boreholes across the Atlantis Massif with the goals of investigating carbon cycling and the presence of life in a zone of active serpentinization. The expedition recovered multiple lithologies including gabbros, basalts, carbonate sands, and serpentinites. A subset of contrasting lithologies were analyzed for apolar lipid content to determine if non-volatile organic molecules can be detected in the oceanic subsurface. The definitive detection and identification of abiotic and biological lipids in the subsurface of an actively serpentinizing system would be a significant step towards understanding a variety of scientific processes, including the evolution of pre-biotic chemistry, microbial habitability, and the global carbon cycle. Given the high potential for contamination during drilling, a suite of materials used in sample collection and processing were also analyzed to characterize their signatures. An n-alkane series ranging from C18 to C30 with δ13C isotopic values of −30.9‰ to −28.8‰ was present in lithologically diverse samples. Multiple lines of evidence point to the rock saw used to remove core exteriors during sample processing as the source of these compounds. Many of the other sample-handling procedures designed to reduce surface contamination were determined to be effective and could be implemented in future projects. This result highlights the value of careful prevention and characterization of contamination to allow for more accurate interpretations of complex and dynamic subsurface processes, and the importance that future reports of these compounds occurs in conjunction with thorough contamination assessments.

Health benefits of dairy lipids and MFGM in infant formula

Human breast milk (HBM) is the gold standard for the early nutrition of the neonates. The best way to improve infant formulas (IFs) is to mimic both the composition and the structure of HBM components. Supplementation of IF with dairy lipids or bovine milk components such as milk fat globule membrane (MFGM), in partial replacement of plant oils that are currently mainly used, has health benefits for infants. In this article, results of clinical studies on the impact of IF supplementation with MFGM and dairy lipids on psychomotor development and infectious disease prevalence in infants are reviewed and supported by recent pre-clinical studies. Numerous human studies have reported beneficial effects of MFGM supplementation on neurocognitive development and protection against infectious agents without deleterious impact on growth. Based on rodent and porcine studies, benefits of adding bovine MFGM and dairy lipids in IFs on gut digestion, physiology and protection against pathogens and inflammatory challenges have also been highlighted. However, more randomized controlled trials testing IF supplementation with bovine milk fat, and specifically apolar lipids and associated glycoproteins, must be performed to increase scientific-based knowledge, address safety concerns, and study its potential programming role of adult health.

F420H2 Is Required for Phthiocerol Dimycocerosate Synthesis in Mycobacteria.

Phthiocerol dimycocerosates (PDIM) are a group of cell surface-associated apolar lipids of Mycobacterium tuberculosis and closely related mycobacteria, such as Mycobacterium bovis and Mycobacterium leprae A characteristic methoxy group of these lipids is generated from the methylation of a hydroxyl group of the direct precursors, the phthiotriols. The precursors arise from the reduction of phthiodiolones, the keto intermediates, by a ketoreductase. The putative phthiodiolone ketoreductase (PKR) is encoded by Rv2951c in M. tuberculosis and BCG_2972c in M. bovis BCG, and these open reading frames (ORFs) encode identical amino acid sequences. We investigated the cofactor requirement of the BCG_2972c protein. A comparative analysis based on the crystallographic structures of similar enzymes identified structural elements for binding of coenzyme F420 and hydrophobic phthiodiolones in PKR. Coenzyme F420 is a deazaflavin coenzyme that serves several key functions in pathogenic and nonpathogenic mycobacteria. We found that an M. bovis BCG mutant lacking F420-dependent glucose-6-phosphate dehydrogenase (Fgd), which generates F420H2 (glucose-6-phosphate + F420 → 6-phosphogluconate + F420H2), was devoid of phthiocerols and accumulated phthiodiolones. When the mutant was provided with F420H2, a broken-cell slurry of the mutant converted accumulated phthiodiolones to phthiocerols; F420H2 was generated in situ from F420 and glucose-6-phosphate by the action of Fgd. Thus, the reaction mixture was competent in reducing phthiodiolones to phthiotriols (phthiodiolones + F420H2 → phthiotriols + F420), which were then methylated to phthiocerols. These results established the mycobacterial phthiodiolone ketoreductase as an F420H2-dependent enzyme (fPKR). A phylogenetic analysis of close homologs of fPKR revealed potential F420-dependent lipid-modifying enzymes in a broad range of mycobacteria. Mycobacterium tuberculosis is the causative agent of tuberculosis, and phthiocerol dimycocerosates (PDIM) protect this pathogen from the early innate immune response of an infected host. Thus, the PDIM synthesis system is a potential target for the development of effective treatments for tuberculosis. The current study shows that a PDIM synthesis enzyme is dependent on the coenzyme F420 F420 is universally present in mycobacteria and absent in humans. This finding expands the number of experimentally validated F420-dependent enzymes in M. tuberculosis to six, each of which helps the pathogen to evade killing by the host immune system, and one of which activates an antituberculosis drug, PA-824. This work also has relevance to leprosy, since similar waxy lipids are found in Mycobacterium leprae.

Skin Absorption of Anions: Part Two. Skin Absorption of Halide Ions.

The purpose of the study was to sort skin penetration of anions with respect to their properties and to assess their mechanisms of penetration. Aqueous solutions of halides at two concentrations were prepared and quantitative penetration studies were carried out for 24h using Franz diffusion cells. The iodide permeation was also measured after blocking of anion channels and transporters to investigate the role of this specific transport. Absorption of halide ions into skin revealed large differences of transport between these anions according to the Hofmeister series. Increasing steady-state fluxes and lag times in the order F(-) < Cl(-) < Br(-) < I(-) were observed in permeation experiments. The steady-state fluxes were proportional to the concentration for each halide ion. Longer lag times for iodide or bromide ions were explained by the ability of such sticky chaotropic anions to interact with apolar lipids especially in the stratum corneum. Inhibiting ion exchangers and channels decreased the flux of iodide ions by 75%, showing the high contribution of the facilitated transport over the passive pathway. Ions transport had contributions coming from passive diffusion through the skin layers and transport mediated by ion channels and binding to ion transporters.

Lipoprotein-Related and Apolipoprotein-Mediated Delivery Systems for Drug Targeting and Imaging.

The integration of lipoprotein-related or apolipoprotein-targeted nanoparticles as pharmaceutical carriers opens new therapeutic and diagnostic avenues in nanomedicine. The concept is to exploit the intrinsic characteristics of lipoprotein particles as being the natural transporter of apolar lipids and fat in human circulation. Discrete lipoprotein assemblies and lipoprotein-based biomimetics offer a versatile nanoparticle platform that can be manipulated and tuned for specific medical applications. This article reviews the possibilities for constructing drug loaded, reconstituted or artificial lipoprotein particles. The advantages and limitations of lipoprotein-based delivery systems are critically evaluated and potential future challenges, especially concerning targeting specificity, concepts for lipoprotein rerouting and design of innovative lipoprotein mimetic particles using apolipoprotein sequences as targeting moieties are discussed. Finally, the review highlights potential medical applications for lipoprotein-based nanoparticle systems in the fields of cardiovascular research, cancer therapy, gene delivery and brain targeting focusing on representative examples from literature.

Membrane homeoviscous adaptation in the piezo-hyperthermophilic archaeon Thermococcus barophilus.

The archaeon Thermococcus barophilus, one of the most extreme members of hyperthermophilic piezophiles known thus far, is able to grow at temperatures up to 103°C and pressures up to 80 MPa. We analyzed the membrane lipids of T. barophilus by high performance liquid chromatography–mass spectrometry as a function of pressure and temperature. In contrast to previous reports, we show that under optimal growth conditions (40 MPa, 85°C) the membrane spanning tetraether lipid GDGT-0 (sometimes called caldarchaeol) is a major membrane lipid of T. barophilus together with archaeol. Increasing pressure and decreasing temperature lead to an increase of the proportion of archaeol. Reversely, a higher proportion of GDGT-0 is observed under low pressure and high temperature conditions. Noticeably, pressure and temperature fluctuations also impact the level of unsaturation of apolar lipids having an irregular polyisoprenoid carbon skeleton (unsaturated lycopane derivatives), suggesting a structural role for these neutral lipids in the membrane of T. barophilus. Whether these apolar lipids insert in the membrane or not remains to be addressed. However, our results raise questions about the structure of the membrane in this archaeon and other Archaea harboring a mixture of di- and tetraether lipids.