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Results for “Membrane Lipid Composition”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 91 records · Page 5
All sourcesNASA NTRSDOE OSTI
DOE OSTI2023

Super-swelling behavior of stacked lipid bilayer systems

Bilayer systems comprising lipid mixtures are the most well-studied model of biological membranes. While the plasma membrane of the cell is a single bilayer, many intra- and extra-cellular biomembranes comprise stacks of bilayers. Most bilayer stacks in nature are periodic, maintaining a precise water layer separation between bilayers. That equilibrium water separation is governed by multiple inter-bilayer forces and is highly responsive. Biomembranes re-configure inter-bilayer spacing in response to temperature, composition, or mass transport cues. In synthetic bilayer systems for applications in cosmetics or topical treatments, control of the hydration level is a critical design handle. Herein we investigate a binary lipid system that leverages key inter-bilayer forces leading to unprecedented levels of aqueous swelling while maintaining a coherent multilamellar form. We found that combining cationic lipids with bicontinuous cubic phase-forming lipids (lipids with positive Gaussian modulus), results in the stabilization of multilamellar phases against repulsive steric forces that typically lead to bilayer delamination at high degrees of swelling. Using ultra-small-angle X-ray scattering alongside confocal laser scanning microscopy, we characterized various super-swelled states of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and glycerol monooleate (GMO) lipids, as well as other analogous systems, at varied concentration and molar ratios. Through these experiments we established swelling profiles of various binary lipid systems that were near-linear with decreasing lipid volume fraction, showing maximum swelling with periodicity well above 200 nanometers.

42 ENGINEERING↗
DOE OSTI2022

HIV Env assembling is tightly modulated by lipid composition and cytoplasmic tail integrity

HIV envelope glycoprotein (Env) is a homotrimeric transmembrane protein which binds to receptors CD4, CCR5- CXCR4, leading to a cascade of conformational changes ultimately resulting in the entrance of the virus into the host cell. Its whole structure comprises an extracellular region, a transmembrane domain and a cytoplasmic region. While many efforts are carried in order to develop an effective vaccine specifically targeting the extracellular domain, less efforts are focus into regions close to the transmembrane region; mostly limited by the lack of structural knowledge within this domain. Thus, it is desirable to have a molecular description of the trimeric association of the transmembrane domain, as well as the membrane properties affecting their structure. We have carried molecular dynamic (MD) simulations of HIV transmembrane region in different lipid environments, mimicking the complex viral membrane. Our results indicate that the lipid environment heavily affects the dynamics and association of the transmembrane helices, modulating its structure. In addition, we have investigated the effect of the cytoplasmic tail (CT). Unexpectedly, this region has a tremendous effect on the lateral organization of the transmembrane. These results clearly highlights the importance of this region in the overall structure of the Env protein and point towards its key role for the in-silico design of effective vaccines towards this domain.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Decoupling copolymer, lipid and carbon nanotube interactions in hybrid, biomimetic vesicles

Bilayer vesicles that mimic a real biological cell can be tailored to carry out a specific function by manipulating the molecular composition of the amphiphiles. These bio-inspired and bio-mimetic structures are increasingly being employed for a number of applications from drug delivery to water purification and beyond. Complex hybrid bilayers are the key building blocks for fully synthetic vesicles that can mimic biological cell membranes, which often contain a wide variety of molecular species. While the assembly and morpholgy of pure phospholid bilayer vesicles is well understood, the functionality and structure dramaticlly changes when copolymer and/or carbon nanotube porins (CNTP) are added. The aim of this study is to understand how the collective molecular interactions within hybrid vesicles affect their nanoscale structure and properties. In situ small and wide angle X-ray scattering (SAXS/WAXS) and molecular dynamics simulations (MD) are used to investigate the morphological effect of molecular interactions between polybutadiene polyethylene oxide, lipids and carbon nanotubes (CNT) within the hybrid vesicle bilayer. Within the lipid/copolymer system, the hybrid bilayer morphology transitions from phase separated lipid and compressed copolymer at low copolymer loadings to a mixed bilayer where opposing lipids are mostly separated from the inner region. This transition begins between 60 wt% and 70 wt%, with full homogenization observed by 80 wt% copolymer. The incorporation of CNT into the hybrid vesicles increases the bilayer thickness and enhances the bilayer symmetry. Analysis of the WAXS and MD indicate that the CNT–dioleoyl interactions are much stronger than the CNT–polybutadiene.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Improved chemical and isotopic labeling of biomembranes in Bacillus subtilis by leveraging CRISPRi inhibition of beta-ketoacyl-ACP synthase (fabF)

Assessing the structure of living microbial cell membranes is a challenging analytical goal. The cell membrane is defined by its transverse structure, an approximately 5 nm-thick selectively permeable bilayer that serves many important cellular functions. Compositionally complex, dynamic, and organized in both the transverse and lateral dimensions, understanding the cell membrane structure—and the role that structure plays in cellular function, communication, and environmental sensing is an active scientific effort. Previously, we have devised a novel isotopic labeling approach for membrane lipids to enable direct in vivo structural studies of the cell membrane in the Gram-positive bacterium, Bacillus subtilis , using small-angle neutron scattering. This was accomplished through a genetic inhibition of fatty acid (FA) degradation (Δ fadN ) and a chemical inhibition of FA biosynthesis using cerulenin, an irreversible inhibitor of type II fatty acid synthases. Here, we improve upon the previous system by introducing a dCas9/sgRNA- fabF complex that blocks transcription of the essential fabF gene when under xylose induction. This leads to greater sensitivity to cerulenin in the mutant strain (JEBS102) and more robust cell growth when supplementary FAs are introduced to the culture medium. A subtle change in FA uptake is noted when compared to the prior labeling strategy. This is seen in the gas chromatography/mass spectrometry (GC/MS) data as a higher ratio of n 16:0 to a 15:0, and manifests in an apparent increase in the membrane thickness determined via neutron scattering. This represents an improved method of isotopic labeling for the cell membrane of Bacillus subtilis; enabling improved investigations of cellular uptake and utilization of FAs, cell membrane structure and organization as a phenotypic response to metabolic and environmental changes.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS1985

Are interpretations of ancient marine temperatures constrained by the presence of ancient marine organisms?

The relationship between marine temperature and marine organisms is investigated. The adaptation of organisms to extreme temperatures is studied; it is observed that chemautotrophic and chemoheterotrophic prokaryotes adapt to 100 C, photoautotrophic prokaryotes to 73 C, and fungi to 60 C. The physiological and molecular factors related to thermal limits in organisms such as enzymes, lipids, or plasma membranes, are examined. Two types of thermal adaptations, resistance and capacity, are detected in organisms. Reasons for species distributions according to temperature barriers are proposed by Read (1967) and Bullock (1955) and are related to enzyme limits. The effects of an organism's composition on thermal stability is analyzed.

Valentine, J. W.↗
DOE OSTI2022

Full scale structural, mechanical and dynamical properties of HIV-1 liposomes

Enveloped viruses are enclosed by a lipid membrane inside of which are all of the components necessary for the virus life cycle; viral proteins, the viral genome and metabolites. Viral envelopes are lipid bilayers that adopt morphologies ranging from spheres to tubes. The envelope is derived from the host cell during viral replication. Thus, the composition of the bilayer depends on the complex constitution of lipids from the host-cell’s organelle(s) where assembly and/or budding of the viral particle occurs. Here, molecular dynamics (MD) simulations of authentic, asymmetric HIV-1 liposomes are used to derive a unique level of resolution of its full-scale structure, mechanics and dynamics. Analysis of the structural properties reveal the distribution of thicknesses of the bilayers over the entire liposome as well as its global fluctuations. Moreover, full-scale mechanical analyses are employed to derive the global bending rigidity of HIV-1 liposomes. Finally, dynamical properties of the lipid molecules reveal important relationships between their 3D diffusion, the location of lipid-rafts and the asymmetrical composition of the envelope. Overall, our simulations reveal complex relationships between the rich lipid composition of the HIV-1 liposome and its structural, mechanical and dynamical properties with critical consequences to different stages of HIV-1’s life cycle.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Vitamin E Acetate Causes Softening of Pulmonary Surfactant Membrane Models

The popularity of electronic cigarettes and vaping products has launched the outbreak of a condition affecting the respiratory system of users, known as electronic-cigarette/vaping-associated lung injury (EVALI). The build-up of vitamin E acetate (VEA), a diluent of some illicit vaping oils, in the bronchoalveolar lavage of patients with EVALI provided circumstantial evidence as a target for investigation. In this work, we provide a fundamental characterization of the interaction of VEA with lung cells and pulmonary surfactant (PS) models to explore the mechanisms by which vaping-related lung injuries may be present. We first confirm the localization and uptake of VEA in pulmonary epithelial cells. Further, as PS is vitally responsible for the biophysical functions of the lungs, we explore the effect of added VEA on three increasingly complex models of PS: dipalmitoylphosphatidylcholine (DPPC), a lipid-only synthetic PS, and the biologically derived extract Curosurf. Using high-resolution techniques of small-angle X-ray scattering, small-angle neutron scattering, neutron spin–echo spectroscopy, and neutron reflectometry, we compare the molecular-scale behaviors of these membranes to the bulk viscoelastic properties of surfactant monolayer films as studied by Langmuir monolayer techniques. While VEA does not obviously alter the structure or organization of PS membranes, a consistent softening of membrane systems—regardless of compositional complexity—provides a biophysical explanation for the respiratory distress associated with EVALI and yields a new perspective on the behavior of the PS system.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Data for MALDI-MS Screening of Microbial Colonies With Isomer Resolution to Select Fatty Acid Desaturase Variants

Creating controlled lipid unsaturation locations in oleochemicals can be a key to many bioengineered products. However, evaluating the effects of modifications to the acyl-ACP desaturase on lipid unsaturation is not currently amenable to high-throughput assays, limiting the scale of redesign efforts to <200 variants. Here, we report a rapid mass spectrometry (MS) assay for profiling the positions of double bonds on membrane lipids produced by Escherichia coli colonies after treatment with ozone gas. By MS measurement of the ozonolysis products of Δ6 and Δ8 isomers of membrane lipids from colonies expressing recombinant Thunbergia alata desaturase, we screened a randomly mutagenized library of the desaturase gene at 5 s per sample. Two variants with altered regiospecificity were isolated, indicated by an increase in 16:1 Δ8 proportion. We also demonstrated the ability of these desaturase variants to influence the membrane composition and fatty acid distribution of E. coli strains deficient in the native acyl-ACP desaturase gene, fabA. Finally, we used the fabA deficient chassis to concomitantly express a non-native acyl-ACP desaturase and a medium-chain thioesterase from Umbellularia californica, demonstrating production of only saturated free fatty acids.

Conversion↗
DOE OSTI2022

Complex Changes in Membrane Lipids Associated with the Modification of Autophagy in Arabidopsis

Autophagy is a conserved mechanism among eukaryotes that degrades and recycles cytoplasmic components. Autophagy is known to influence the plant metabolome, including lipid content; however, its impact on the plant lipidome is not fully understood, and most studies have analyzed a single or few mutants defective in autophagy. To gain more insight into the effect of autophagy on lipid concentrations and composition, we quantitatively profiled glycerolipids from multiple Arabidopsis thaliana mutants altered in autophagy and compared them with wild-type seedlings under nitrogen replete (+N; normal growth) and nitrogen starvation (−N; autophagy inducing) conditions. Mutants include those in genes of the core autophagy pathway, together with other genes that have been reported to affect autophagy. Using Matrix-Assisted Laser Desorption/Ionization—Mass Spectrometry (MALDI-MS), we imaged the cellular distribution of specific lipids in situ and demonstrated that autophagy and nitrogen treatment did not affect their spatial distribution within Arabidopsis seedling leaves. We observed changes, both increases and decreases, in the relative amounts of different lipid species in the mutants compared to WT both in +N and −N conditions, although more changes were seen in −N conditions. The relative amounts of polyunsaturated and very long chain lipids were significantly reduced in autophagy-disrupted mutants compared to WT plants. Collectively, our results provide additional evidence that autophagy affects plant lipid content and that autophagy likely affects lipid properties such as chain length and unsaturation.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Dynamics and activation of membrane-bound B cell receptor assembly

B-cell receptor (BCR) complexes are expressed on the surface of a B-cell and are critical in antigen recognition and modulating the adaptive immune response. Even though the relevance of antibodies has been known for almost a hundred years, the antigen-dependent activation mechanism of B-cells has remained elusive. Several models have been proposed for BCR activation, including cross-linking, conformation-induced oligomerization, and dissociation activation models. Recently, the first cryo-EM structures of the human B-cell antigen receptor of the IgM and IgG isotypes have been published that validates the asymmetric organization of the BCR complex. Here, we carry out extensive molecular dynamics simulations to probe the conformational changes upon antigen binding and the influence of the membrane lipids. We identify two critical dynamical events that could be associated with antigen-dependent activation of BCR. First, antigen binding causes increased flexibility in regions distal to the antigen binding site. Second, antigen binding alters the rearrangement of IgM transmembrane helices, including the relative interaction of Igα/Igβ that mediates intracellular signaling. Furthermore, these transmembrane rearrangements lead to changes in localized lipid composition. Our work indirectly supports the conformational-change induced models of BCR activation and contributes to the understanding of the antigen-dependent activation mechanism of BCRs.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

BefA, a microbiota-secreted membrane disrupter, disseminates to the pancreas and increases β cell mass

Microbiome dysbiosis is a feature of diabetes, but how microbial products influence insulin production is poorly understood. Here, we report the mechanism of BefA, a microbiome-derived protein that increases proliferation of insulin-producing β cells during development in gnotobiotic zebrafish and mice. BefA disseminates systemically by multiple anatomic routes to act directly on pancreatic islets. We detail BefA’s atomic structure, containing a lipid-binding SYLF domain, and demonstrate that it permeabilizes synthetic liposomes and bacterial membranes. A BefA mutant impaired in membrane disruption fails to expand β cells, whereas the pore-forming host defense protein, Reg3, stimulates β cell proliferation. Our work demonstrates that membrane permeabilization by microbiome-derived and host defense proteins is necessary and sufficient for β cell expansion during pancreas development, potentially connecting microbiome composition with diabetes risk.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Optimization of peptide amphiphile-lipid raft interaction by changing peptide amphiphile lipophilicity

Various peptide amphiphile (PA) molecules have been developed to promote bone regeneration. Previously we discovered that a peptide amphiphile with a palmitic acid tail (C 16 ) attenuates the signaling threshold of leucine-rich amelogenin peptide (LRAP)-mediated Wnt activation by increasing membrane lipid raft mobility. In the current study, we found that treatment of murine ST2 cells with an inhibitor (Nystatin) or Caveolin-1-specific siRNA abolishes the effect of C 16 PA, indicating that Caveolin-mediated endocytosis is required. Here, to determine whether hydrophobicity of the PA tail plays a role in its signaling effect, we modified the length of the tail (C 12 , C 16 and C 22 ) or composition (cholesterol). While shortening the tail (C 12 ) decreased the signaling effect, lengthening the tail (C 22 ) had no prominent effect. On the other hand, the cholesterol PA displayed a similar function as the C 16 PA at the same concentration of 0.001% w/v. Interestingly, a higher concentration of C 16 PA (0.005%) is cytotoxic while cholesterol PA at the higher concentration (0.005%) is well-tolerated by cells. Use of the cholesterol PA at 0.005% enabled a further reduction of the signaling threshold of LRAP to 0.20 nM, compared to 0.25 nM at 0.001%. Caveolin-mediated endocytosis is also required for cholesterol PA, as evidenced by Caveolin-1 siRNA knockdown experiments. We further demonstrated that the noted effects of cholesterol PA are also observed in human bone marrow mesenchymal stem cells (BMMSCs). Taken together, these results indicate that the cholesterol PA modulates lipid raft/caveolar dynamics, thereby increasing receptor sensitivity for activation of canonical Wnt signaling.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Structural insights into the modulation of coronavirus spike tilting and infectivity by hinge glycans

Abstract Coronavirus spike glycoproteins presented on the virion surface mediate receptor binding, and membrane fusion during virus entry and constitute the primary target for vaccine and drug development. How the structure dynamics of the full-length spikes incorporated in viral lipid envelope correlates with the virus infectivity remains poorly understood. Here we present structures and distributions of native spike conformations on vitrified human coronavirus NL63 (HCoV-NL63) virions without chemical fixation by cryogenic electron tomography (cryoET) and subtomogram averaging, along with site-specific glycan composition and occupancy determined by mass spectrometry. The higher oligomannose glycan shield on HCoV-NL63 spikes than on SARS-CoV-2 spikes correlates with stronger immune evasion of HCoV-NL63. Incorporation of cryoET-derived native spike conformations into all-atom molecular dynamic simulations elucidate the conformational landscape of the glycosylated, full-length spike that reveals a role of hinge glycans in modulating spike bending. We show that glycosylation at N1242 at the upper portion of the stalk is responsible for the extensive orientational freedom of the spike crown. Subsequent infectivity assays implicated involvement of N1242-glyan in virus entry. Our results suggest a potential therapeutic target site for HCoV-NL63.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS1992

The effects of growth temperature on the methyl sterol and phospholipid fatty acid composition of Methylococcus capsulatus (Bath)

Growth of Methylococcus capsulatus (Bath) at temperatures ranging from 30 to 50 C resulted in changes to the whole cell lipid constituents. As temperature was lowered, the overall proportion of hexadecenoic acid (C16:1) increased, and the relative proportions of the Delta9, Delta10, and Delta11 C16:1 double bond positional isomers changed. Methyl sterol content also increased as the growth temperature was lowered. The highest amounts of methyl sterol were found in 30 C cells and the lowest in 50 C cells (sterol-phospholipid ratios of 0.077 and 0.013, respectively). The data are consistent with a membrane modulating role for the sterol produced by this prokaryotic organism.

Jahnke, Linda L.↗
NASA NTRS1992

The effects of growth temperature on the methyl sterol and phospholipid fatty acid composition of Methylococcus capsulatus (Bath)

Growth of Methylococcus capsulatus (Bath) at temperatures ranging from 30 to 50 degrees C resulted in changes to the whole cell lipid constituents. As temperature was lowered, the overall proportion of hexadecenoic acid (C16:1) increased, and the relative proportions of the delta 9, delta 10 and delta 11 C16:1 double bond positional isomers changed. Methyl sterol content also increased as the growth temperature was lowered. The highest amounts of methyl sterol were found in 30 degrees C cells and the lowest in 50 degrees C cells (sterol-phospholipid ratios of 0.077 and 0.013, respectively). The data are consistent with a membrane modulating role for the sterol produced by this prokaryotic organism.

Jahnke, L. L.↗
NASA NTRS2011

The Importance of Sample Return in Establishing Chemical Evidence for Life on Mars or Other Solar System Bodies

The search for evidence of life on Mars and elsewhere will continue to be one of the primary goals of NASA s robotic exploration program over the next decade. NASA and ESA are currently planning a series of robotic missions to Mars with the goal of understanding its climate, resources, and potential for harboring past or present life. One key goal will be the search for chemical biomarkers including complex organic compounds important in life on Earth. These include amino acids, the monomer building blocks of proteins and enzymes, nucleobases and sugars which form the backbone of DNA and RNA, and lipids, the structural components of cell membranes. Many of these organic compounds can also be formed abiotically as demonstrated by their prevalence in carbonaceous meteorites [1], though, their molecular characteristics may distinguish a biological source [2]. It is possible that in situ instruments may reveal such characteristics, however, return of the right sample (i.e. one with biosignatures or having a high probability of biosignatures) to Earth would allow for more intensive laboratory studies using a broad array of powerful instrumentation for bulk characterization, molecular detection, isotopic and enantiomeric compositions, and spatially resolved chemistry that may be required for confirmation of extant or extinct Martian life. Here we will discuss the current analytical capabilities and strategies for the detection of organics on the Mars Science Laboratory (MSL) using the Sample Analysis at Mars (SAM) instrument suite and how sample return missions from Mars and other targets of astrobiological interest will help advance our understanding of chemical biosignatures in the solar system.

Glavin, D. P.↗
DOE OSTI2021

Whole-soil warming decreases abundance and modifies the community structure of microorganisms in the subsoil but not in surface soil

Abstract. The microbial community composition in subsoils remains understudied, and it is largely unknown whether subsoil microorganisms show a similar response to global warming as microorganisms at the soil surface do. Since microorganisms are the key drivers of soil organic carbon decomposition, this knowledge gap causes uncertainty in the predictions of future carbon cycling in the subsoil carbon pool (> 50 % of the soil organic carbon stocks are below 30 cm soil depth). In the Blodgett Forest field warming experiment (California, USA) we investigated how +4 ∘C warming in the whole-soil profile to 100 cm soil depth for 4.5 years has affected the abundance and community structure of microorganisms. We used proxies for bulk microbial biomass carbon (MBC) and functional microbial groups based on lipid biomarkers, such as phospholipid fatty acids (PLFAs) and branched glycerol dialkyl glycerol tetraethers (brGDGTs). With depth, the microbial biomass decreased and the community composition changed. Our results show that the concentration of PLFAs decreased with warming in the subsoil (below 30 cm) by 28 % but was not affected in the topsoil. Phospholipid fatty acid concentrations changed in concert with soil organic carbon. The microbial community response to warming was depth dependent. The relative abundance of Actinobacteria increased in warmed subsoil, and Gram+ bacteria in subsoils adapted their cell membrane structure to warming-induced stress, as indicated by the ratio of anteiso to iso branched PLFAs. Our results show for the first time that subsoil microorganisms can be more affected by warming compared to topsoil microorganisms. These microbial responses could be explained by the observed decrease in subsoil organic carbon concentrations in the warmed plots. A decrease in microbial abundance in warmed subsoils might reduce the magnitude of the respiration response over time. The shift in the subsoil microbial community towards more Actinobacteria might disproportionately enhance the degradation of previously stable subsoil carbon, as this group is able to metabolize complex carbon sources.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2022

Ultrastructure of Organohalide-Respiring Dehalococcoidia Revealed by Cryo-Electron Tomography

Dehalococcoides mccartyi (Dhc) and Dehalogenimonas spp. (Dhgm) are members of the class Dehalococcoidia, phylum Chloroflexi, characterized by streamlined genomes and a strict requirement for organohalogens as electron acceptors. Here, we used cryo-electron tomography to reveal morphological and ultrastructural features of Dhc strain BAV1 and “Candidatus Dehalogenimonas etheniformans” strain GP cells at unprecedented resolution. Dhc cells were irregularly shaped discs (890 ± 110 nm long, 630 ± 110 nm wide, and 130 ± 15 nm thick) with curved and straight sides that intersected at acute angles, whereas Dhgm cells appeared as slightly flattened cocci (760 ± 85 nm). The cell envelopes were composed of a cytoplasmic membrane (CM), a paracrystalline surface layer (S-layer) with hexagonal symmetry and ~22-nm spacing between repeating units, and a layer of unknown composition separating the CM and the S-layer. Cell surface appendages were only detected in Dhc cells, whereas both cell types had bundled cytoskeletal filaments. Repetitive globular structures, ~5 nm in diameter and ~9 nm apart, were observed associated with the outer leaflet of the CM. We hypothesized that those represent organohalide respiration (OHR) complexes and estimated ~30,000 copies per cell. In Dhgm cultures, extracellular lipid vesicles (20 to 110 nm in diameter) decorated with putative OHR complexes but lacking an S-layer were observed. Furthermore, the new findings expand our understanding of the unique cellular ultrastructure and biology of organohalide-respiring Dehalococcoidia.

59 BASIC BIOLOGICAL SCIENCES↗