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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 145 records · Page 8
All sourcesNASA NTRSDOE OSTI
DOE OSTI2014

Systematically programmed adaptive evolution reveals potential role of carbon and nitrogen pathways during lipid accumulation in Chlamydomonas reinhardtii

Background: The concept of adaptive evolution implies underlying genetic mutations conferring a selective advantage to an organism under particular environmental conditions. Thus, a flow cytometry-based strategy was used to study the adaptive evolution in Chlamydomonas reinhardtii wild-type strain CC124 and starchless mutant sta6-1 cells, with respect to lipid metabolism under nitrogen-(N) depleted and -replete conditions. Results: The successive sorting and regeneration of the top 25,000 high-lipid content cells of CC124 and sta6-1, combined with nitrogen starvation, led to the generation of a new population with an improved lipid content when compared to the original populations (approximately 175% and 50% lipid increase in sta6-1 and CC124, respectively). During the adaptive evolution period, the major fatty acid components observed in cells were C16:0, C16:1, C18:0, and C18:1-3, and elemental analysis revealed that cellular carbon to nitrogen ratio increased at the end of adaptive evolution period In order to gain an insight into highly stimulated intracellular lipid accumulation in CC124 and sta6-1 resulting from the adaptive evolution, proteomics analyses of newly generated artificial high-lipid content populations were performed. Functional classifications showed the heightened regulation of the major chlorophyll enzymes, and the enzymes involved in carbon fixation and uptake, including chlorophyll-ab-binding proteins and Rubisco activase. The key control protein (periplasmic L-amino acid oxidase (LAO1)) of carbon-nitrogen integration was specifically overexpressed. Glutathione-S-transferases and esterase, the enzymes involved in lipid-metabolism and lipid-body associated proteins, were also induced during adaptive evolution. Conclusions: Adaptive evolution results demonstrate the potential role of photosynthesis in terms of carbon partitioning, flux, and fixation and carbon-nitrogen metabolism during lipid accumulation in microalgae. This strategy can be used as a new tool to develop C. reinhardtii strains and other microalgal strains with desired phenotypes such as high lipid accumulation.

09 BIOMASS FUELS↗
DOE OSTI2024

Data for Hydrothermal Conditioning of Oleaginous Yeast Cells to Enable Recovery of Lipids as Potential Drop-in Fuel Precursors

Lipids produced using oleaginous yeast cells are an emerging feedstock to manufacture commercially valuable oleochemicals ranging from pharmaceuticals to lipid-derived biofuels. Production of biofuels using oleaginous yeast is a multistep procedure that requires yeast cultivation and harvesting, lipid recovery, and conversion of the lipids to biofuels. The quantitative recovery of the total intracellular lipid from the yeast cells is a critical step during the development of a bioprocess. Their rigid cell walls often make them resistant to lysis. The existing methods include mechanical, chemical, biological and thermochemical lysis of yeast cell walls followed by solvent extraction. In this study, an aqueous thermal pretreatment was explored as a method for lysing the cell wall of the oleaginous yeast Rhodotorula toruloides for lipid recovery. Hydrothermal pretreatment for 60 min at 121 °C with a dry cell weight of 7% (w/v) in the yeast slurry led to a recovery of 84.6 ± 3.2% (w/w) of the total lipids when extracted with organic solvents. The conventional sonication and acid-assisted thermal cell lysis led to a lipid recovery yield of 99.8 ± 0.03% (w/w) and 109.5 ± 1.9% (w/w), respectively. The fatty acid profiles of the hydrothermally pretreated cells and freeze-dried control were similar, suggesting that the thermal lysis of the cells did not degrade the lipids. This work demonstrates that hydrothermal pretreatment of yeast cell slurry at 121 °C for 60 min is a robust and sustainable method for cell conditioning to extract intracellular microbial lipids for biofuel production and provides a baseline for further scale-up and process integration.

Conversion↗
DOE OSTI2020

Data from Biodiesel Production from Engineered Sugarcane Lipids under Uncertain Feedstock Compositions: Process Design and Techno-Economic Analysis

In this study, different process schemes were designed and evaluated for biodiesel production from engineered cane lipids with uncertain fatty acid compositions. Four different process schemes were compared under (i) thermal glycerolysis and (ii) enzymatic glycerolysis approaches. These schemes were based on the biodiesel yield and economic indicators such as the net present value (NPV) and the minimum selling price (MSP) of biodiesel. A scheme with polar lipid separation under thermal glycerolysis resulted in the maximum NPV ($96.5 million) and minimum MSP ($1107/ton biodiesel), respectively. Through local sensitivity analysis, it was concluded that the cane lipid percentage is the most significant factor influencing process economics. A conjoint analysis of the lipid procurement price and cane lipid percent suggested that 15% cane lipids with a low lipid procurement price ($0.536/kg) results in a positive NPV. When the cane lipid price is higher (>$0.80/kg), a 20% lipid content should be considered to achieve a positive NPV. At 20% cane lipids, the worst-case and best-case scenarios were evaluated by analyzing the interplay of the three most important parameters, The best-case scenario revealed that the minimum NPV under any process scheme could yield more than $100 million (or MSP: $0.80/L), and the worst-case analysis showed that losses incurred by the plant could be as high as $80 million (MSP: $1.36/L). A Monte Carlo simulation indicated that there is a 70% chance of the plant being profitable (NPV > 0).

Conversion↗
DOE OSTI2017

A robust and efficient method for the extraction of plant extracellular surface lipids as applied to the analysis of silks and seedling leaves of maize

Aerial plant organs possess a diverse array of extracellular surface lipids, including both non-polar and amphipathic constituents that collectively provide a primary line of defense against environmental stressors. Extracellular surface lipids on the stigmatic silks of maize are composed primarily of saturated and unsaturated linear hydrocarbons, as well as fatty acids, and aldehydes. To efficiently extract lipids of differing polarities from maize silks, five solvent systems (hexanes; hexanes:diethyl ether (95:5); hexanes:diethyl ether (90:10); chloroform:hexanes (1:1) and chloroform) were tested by immersing fresh silks in solvent for different extraction times. Surface lipid recovery and the relative composition of individual constituents were impacted to varying degrees depending on solvent choice and duration of extraction. Analyses were performed using both silks and leaves to demonstrate the utility of the solvent- and time-optimized protocol in comparison to extraction with the commonly used chloroform solvent. Overall, the preferred solvent system was identified as hexanes:diethyl ether (90:10), based on its effectiveness in extracting surface hydrocarbons and fatty acids as well as its reduced propensity to extract presumed internal fatty acids. Metabolite profiling of wildtype and glossy1 seedlings, which are impaired in surface lipid biosynthesis, demonstrated the ability of the preferred solvent to extract extracellular surface lipids rich in amphipathic compounds (aldehydes and alcohols). In addition to the expected deficiencies in dotriacontanal and dotriacontan-1-ol for gl1 seedlings, an unexpected increase in fatty acid recovery was observed in gl1 seedlings extracted in chloroform, suggesting that chloro-form extracts lipids from internal tissues of gl1 seedlings. This highlights the importance of extraction method when evaluating mutants that have altered cuticular lipid compositions. Lastly, metabolite profiling of silks from maize inbreds B73 and Mo17, exposed to different environments and harvested at different ages, revealed differences in hydrocarbon and fatty acid composition, demonstrating the dynamic nature of surface lipid accumulation on silks.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2018

Lipidomic study reveals the effect of morphological variation and other metabolite interactions on the lipid composition in various cultivars of Bok choy

Bok choy is an important Brassica vegetable which is also known for its wide range of cultivars that differ in their appearance, leaf color, size and shape. For the purpose to investigate the effect of these phenotypic differences on their lipid composition, seven morphotypes of NHCC (Suzhouqing, Aijaohuang, Wutacai, Yellowrose, Ziluolan, Xiangqingcai and Zicaitai) were selected for this study. For this reason, extensive metabolic approach was adopted which was mainly focused on lipidomics. The overall metabolic position of lipids was determined and the isolated lipid compounds were characterized on the basis of their lipid classes. Moreover, discriminative analysis was applied to monitor the distribution pattern of lipid in different cultivars. Aijiaohuang was the leading cultivar which contained highest lipid levels, whereas least proportion was found in Zicaitai. We proposed that leaf color might have an effect on the lipid composition such as purple cultivars were dominated in glycerophopholipids, light green in fatty acids and dark green were rich in glycerolipids. The level of metabolites differed greatly among different genotypes. Lipid-metabolite interactions revealed the positive correlation of lipids with flavonoid and hydroxycinnamoyl derivatives, whereas negative correlation was noticed in case of phenylamines. This is the first comprehensive study based on lipidomics in order to evaluate the substantial impact of various phenotypes on the metabolic composition of NHCC.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2025

Anionic Lipids Regulate the Light-Harvesting Complex 1-Reaction Center Photocycle in Purple Bacteria

Photosynthetic purple bacteria can capture and convert sunlight with a remarkable, nearly 100% quantum efficiency. The light-harvesting complex 1-reaction center (LH1-RC) core complex is the membrane complex fundamentally responsible for solar energy conversion. LH1-RC has a highly conserved surrounding lipid composition known to favor anionic lipids for an unknown function. Here, in this work, we compared experimentally the rate of LH1-to-RC energy transfer in detergent, membrane nanodiscs with varying lipid compositions, purified membrane fragments, and live cells. The energy transfer rate indicated that RC turnover decreased in neutral lipids, yet was partially restored in anionic lipids, revealing an unexpected lipid dependence. In complementary molecular dynamics simulations, the anionic lipid cardiolipin showed electrostatic interactions with LH1-RC that may mediate quinone exchange, providing a mechanism for the observed lipid dependence. Overall, these results revealed that anionic lipids facilitate LH1-RC redox cycling, identifying a functional role for membrane composition in photosynthetic solar energy conversion.

bacteria↗
DOE OSTI2021

Molecular basis for lipid recognition by the prostaglandin D 2 receptor CRTH2

Significance Many amphipathic lipids, including cannabinoids, lysophospholipids, prostanoids, and leukotrienes, bind to G protein–coupled receptors (GPCRs) through the lipid bilayer. How these lipid ligands get anchored to their receptors and enter ligand-binding pockets is largely elusive. Our results revealed a distinctive lipid recognition mechanism for the prostaglandin D 2 (PGD 2 ) receptor CRTH2 that is not shared by other prostanoid receptors. Based on the structural analysis, we propose two representative binding modes of lipids in GPCRs. We also identified critical structural motifs and conformational changes of CRTH2 for capturing lipids from the lipidic environment and lipid transition to the binding pocket, thereby offering unprecedented molecular insight into the dynamic lipid-binding processes for GPCRs.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2017

Lateral pressure profile in lipid membranes with curvature: Analytical calculation

An analytical expression is obtained for the lateral pressure profile in the hydrophobic part of a lipid bilayer of finite curvature. Calculations are carried out within a microscopic model of a lipid bilayer, according to which the energy of a lipid chain represents the energy of a flexible string of finite thickness and the interaction between lipid chains is considered as a steric (entropic) repulsion. This microscopic model allows one to obtain an expression for the distribution of lateral pressure in membranes with given curvature if one considers the bending of a membrane as a small deviation from a flat conformation and applies perturbation theory in the small parameter L{sub 0}J, where L{sub 0} is the hydrophobic thickness of a monolayer and J is the mean curvature of the lipid bilayer. The resulting pressure profile depends on the microscopic parameters of the lipid chain: the bending modulus of the lipid chain, incompressible area per lipid chain, and the thickness of a flat monolayer. The coefficient of entropic repulsion between lipids is calculated self-consistently. The analytical results obtained for the lateral pressure distribution are in qualitative agreement with molecular dynamic simulations.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗
DOE OSTI2018

Lipid accumulation from glucose and xylose in an engineered, naturally oleaginous strain of Saccharomyces cerevisiae

Saccharomyces cerevisiae, a well-known industrial yeast for alcoholic fermentation, is not historically known to accumulate lipids. Four S. cerevisiae strains used in industrial applications were screened for their ability to accumulate neutral lipids. Only one, D5A, was found to accumulate up to 20% dry cell weight (dcw) lipids. This strain was further engineered by knocking out ADP-activated serine/threonine kinase (SNF1) which increased lipid accumulation to 35% dcw lipids. In addition, we engineered D5A to utilize xylose and found that D5A accumulates up to 37% dcw lipids from xylose as the sole carbon source. Further we over-expressed different diacylglycerol acyltransferase (DGA1) genes and boosted lipid accumulation to 50%. Fatty acid speciation showed that 94% of the extracted lipids consisted of 5 fatty acid species, C16:0 (palmitic), C16:1n7 (palmitoleic), C18:0 (stearic), C18:1n7 (vaccenic), and C18:1n9 (oleic), while the relative distributions changed depending on growth conditions. In addition, this strain accumulated lipids concurrently with ethanol production.

09 BIOMASS FUELS↗
DOE OSTI2024

High-resolution ion mobility based on traveling wave structures for lossless ion manipulation resolves hidden lipid features

Abstract High-resolution ion mobility (resolving power > 200) coupled with mass spectrometry (MS) is a powerful analytical tool for resolving isobars and isomers in complex samples. High-resolution ion mobility is capable of discerning additional structurally distinct features, which are not observed with conventional resolving power ion mobility (IM, resolving power ~ 50) techniques such as traveling wave IM and drift tube ion mobility (DTIM). DTIM in particular is considered to be the “gold standard” IM technique since collision cross section (CCS) values are directly obtained through a first-principles relationship, whereas traveling wave IM techniques require an additional calibration strategy to determine accurate CCS values. In this study, we aim to evaluate the separation capabilities of a traveling wave ion mobility structures for lossless ion manipulation platform integrated with mass spectrometry analysis (SLIM IM-MS) for both lipid isomer standards and complex lipid samples. A cross-platform investigation of seven subclass-specific lipid extracts examined by both DTIM-MS and SLIM IM-MS showed additional features were observed for all lipid extracts when examined under high resolving power IM conditions, with the number of CCS-aligned features that resolve into additional peaks from DTIM-MS to SLIM IM-MS analysis varying between 5 and 50%, depending on the specific lipid sub-class investigated. Lipid CCS values are obtained from SLIM IM ( TW(SLIM) CCS) through a two-step calibration procedure to align these measurements to within 2% average bias to reference values obtained via DTIM ( DT CCS). A total of 225 lipid features from seven lipid extracts are subsequently identified in the high resolving power IM analysis by a combination of accurate mass-to-charge, CCS, retention time, and linear mobility-mass correlations to curate a high-resolution IM lipid structural atlas. These results emphasize the high isomeric complexity present in lipidomic samples and underscore the need for multiple analytical stages of separation operated at high resolution. Graphical abstract

Reardon, Allison R. (ORCID:0000000165830134)↗
DOE OSTI2017

Aspirin suppresses the abnormal lipid metabolism in liver cancer cells via disrupting an NFκB-ACSL1 signaling

Abnormal lipid metabolism is a hallmark of tumorigenesis. Hence, the alterations of metabolism enhance the development of hepatocellular carcinoma (HCC). Aspirin is able to inhibit the growth of cancers through targeting nuclear factor κB (NF-κB). However, the role of aspirin in disrupting abnormal lipid metabolism in HCC remains poorly understood. In this study, we report that aspirin can suppress the abnormal lipid metabolism of HCC cells through inhibiting acyl-CoA synthetase long-chain family member 1 (ACSL1), a lipid metabolism-related enzyme. Interestingly, oil red O staining showed that aspirin suppressed lipogenesis in HepG2 cells and Huh7 cells in a dose-dependent manner. In addition, aspirin attenuated the levels of triglyceride and cholesterol in the cells, respectively. Strikingly, we identified that aspirin was able to down-regulate ACSL1 at the levels of mRNA and protein. Moreover, we validated that aspirin decreased the nuclear levels of NF-κB in HepG2 cells. Mechanically, PDTC, an inhibitor of NF-κB, could down-regulate ACSL1 at the levels of mRNA and protein in the cells. Functionally, PDTC reduced the levels of lipid droplets, triglyceride and cholesterol in HepG2 cells. Thus, we conclude that aspirin suppresses the abnormal lipid metabolism in HCC cells via disrupting an NFκB-ACSL1 signaling. Our finding provides new insights into the mechanism by which aspirin inhibits abnormal lipid metabolism of HCC. Therapeutically, aspirin is potentially available for HCC through controlling abnormal lipid metabolism. - Highlights: • Aspirin inhibits the levels of liquid droplets, triglyceride and cholesterol in HCC cells. • Aspirin is able to down-regulate ACSL1 in HCC cells. • NF-κB inhibitor PDTC can down-regulate ACSL1 and reduces lipogenesis in HCC cells. • Aspirin suppresses the abnormal lipid metabolism in HCC cells via disrupting an NFκB-ACSL1 signaling.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Biosynthetic machinery for C25,C25-diether archaeal lipids from the hyperthermophilic archaeon Aeropyrum pernix

Highlights: • A. pernix enzymes involved in C25,C25-diether lipid biosynthesis were identified. • Granylfarnesyl reductase catalyzed saturation of C25,C25-diether lipid. • E. coli harboring archaeal genes produced the hyperthermophile-specific lipid. Archaea that thrive in harsh environments usually produce membrane lipids with specific structures such as bipolar tetraether lipids. Only a few genera of archaea, which are hyperthermophiles or halophiles, are known to utilize diether lipids with extended, C{sub 25} isoprenoid hydrocarbon chains. In the present study, we identify two prenyltransferases and a prenyl reductase responsible for the biosynthesis of C{sub 25},C{sub 25}-diether lipids in the hyperthermophilic archaeon Aeropyrum pernix. These enzymes are more specific to C{sub 25} isoprenoid chains than to C{sub 20} chains, which are used for the biosynthesis of ordinary C{sub 20},C{sub 20}-diether archaeal lipids. The recombinant expression of these enzymes with two known archaeal enzymes allows the production of C{sub 25},C{sub 25}-diether archaeal lipids in the cells of Escherichia coli.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Models of lipid droplets growth and fission in adipocyte cells

Lipid droplets (LD) are spherical cellular inclusion devoted to lipids storage. It is well known that excessive accumulation of lipids leads to several human worldwide diseases like obesity, type 2 diabetes, hepatic steatosis and atherosclerosis. LDs' size range from fraction to one hundred of micrometers in adipocytes and is related to the lipid content, but their growth is still a puzzling question. It has been suggested that LDs can grow in size due to the fusion process by which a larger LD is obtained by the merging of two smaller LDs, but these events seems to be rare and difficult to be observed. Many other processes are thought to be involved in the number and growth of LDs, like the de novo formation and the growth through additional neutral lipid deposition in pre-existing droplets. Moreover the number and size of LDs are influenced by the catabolism and the absorption or interaction with other organelles. The comprehension of these processes could help in the confinement of the pathologies related to lipid accumulation. In this study the LDs' size distribution, number and the total volume of immature (n=12), mature (n=12, 10-days differentiated) and lipolytic (n=12) 3T3-L1 adipocytes were considered. More than 11,000 LDs were measured in the 36 cells after Oil Red O staining. In a previous work Monte Carlo simulations were used to mimic the fusion process alone between LDs. We found that, considering the fusion as the only process acting on the LDs, the size distribution in mature adipocytes can be obtained with numerical simulation starting from the size distribution in immature cells provided a very high rate of fusion events. In this paper Monte Carlo simulations were developed to mimic the interaction between LDs taking into account many other processes in addition to fusion (de novo formation and the growth through additional neutral lipid deposition in pre-existing droplets) in order to reproduce the LDs growth and we also simulated the catabolism (fission and the decrease through neutral lipid exit from pre-existing droplets) to reproduce their size reduction observed in lipolytic conditions. The results suggest that each single process, considered alone, can not be considered the only responsible for the size variation observed, but more than one of them, playing together, can quite well reproduce the experimental data. - Highlights: The growth and fission of the lipid droplets (LDs) were computationally simulated. To write and test the growth and fission models more than 110,000 LDs were measured. The usual processes considered alone, are not able to justify the experimental data. Some processes, playing together, can explain the growth and fission.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2019

Exploiting the Semidestructive Nature of Gas Cluster Ion Beam Time-of-Flight Secondary Ion Mass Spectrometry Imaging for Simultaneous Localization and Confident Lipid Annotations

Lipids have been considered as key players in cell signaling and disease. Information on their location and distribution within a biological system, under varying conditions, is necessary to understand the contributions of different lipid species to an altered phenotype. Imaging mass spectrometry techniques, such as time-of-flight secondary ion mass spectrometry (ToF-SIMS) and matrix-assisted laser desorption/ionization (MALDI), are capable of revealing global lipid distributions in tissues in an untargeted fashion. Yet, to confidently identify the species present in a sample, orthogonal analyses like tandem MS (MS/MS) are often required. This can be accomplished by bulk sample analysis with liquid chromatography (LC)-MS/MS, which can provide confident lipid identifications, at the expense of losing location-specific information. Here, using planarian flatworms as a model system, we demonstrate that imaging gas cluster ion beam (GCIB)-ToF-SIMS has the unique capability to simultaneously detect, identify, and image lipid species with subcellular resolution in tissue sections. The parallel detection of both, intact lipids and their respective fragments, allows for unique identification of some species without the need of performing an additional orthogonal MS/MS analysis. This was accomplished by correlating intact lipid and associated fragment SIMS images. The lipid assignments, respective fragment identities, and locations gathered from ToF-SIMS data were confirmed via LC-MS/MS on lipid extracts and ultrahigh mass resolution MALDI-MS imaging. Together, these data show that the semidestructive nature of ToF-SIMS can be utilized advantageously to enable both confident molecular annotations and to determine the locations of species within a biological sample.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2018

Reorganization of Ternary Lipid Mixtures of Nonphosphorylated Phosphatidylinositol Interacting with Angiomotin

Phosphatidylinositol (PI) lipids are necessary for many cellular signaling pathways of membrane associated proteins, such as angiomotin (Amot). The Amot family regulates cellular polarity, growth, and migration. Given the low concentration of PI lipids in these membranes, it is likely that such protein-membrane interactions are stabilized by lipid domains or small lipid clusters. By small-angle X-ray scattering, we show that nonphosphorylated PI lipids induce lipid demixing in ternary mixtures of phosphatidylcholine (PC) and phosphatidylethanolamine (PE), likely because of preferential interactions between the head groups of PE and PI. These results were obtained in the presence of buffer containing tris(hydroxymethyl)aminomethane, 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid, NaCl, ethyl-enediaminetetraacetic acid, dithiothreitol, and benzamidine at pH 8.0 that in previous work showed an ability to cause PC to phase separate but are necessary to stabilize Amot for in vitro experimentation. Collectively, this provided a framework for determining the effect of Amot on lipid organization. Using fluorescence spectroscopy, we were able to show that the association of Amot with this lipid platform causes significant reorganization of the lipid into a more homogenous structure. As a result, this reorganization mechanism could be the basis for Amot membrane association and fusogenic activity previously described in the literature and should be taken into consideration in future protein-membrane interaction studies.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2016

Crowding-induced mixing behavior of lipid bilayers: Examination of mixing energy, phase, packing geometry, and reversibility

In an effort to develop a general thermodynamic model from first-principles to describe the mixing behavior of lipid membranes, we examined lipid mixing induced by targeted binding of small (Green Fluorescent Protein (GFP)) and large (nanolipoprotein particles (NLPs)) structures to specific phases of phase-separated lipid bilayers. Phases were targeted by incorporation of phase-partitioning iminodiacetic acid (IDA)-functionalized lipids into ternary lipid mixtures consisting of DPPC, DOPC, and cholesterol. GFP and NLPs, containing histidine tags, bound the IDA portion of these lipids via a metal, Cu 2+ , chelating mechanism. In giant unilamellar vesicles (GUVs), GFP and NLPs bound to the Lo domains of bilayers containing DPIDA, and bound to the Ld region of bilayers containing DOIDA. At sufficiently large concentrations of DPIDA or DOIDA, lipid mixing was induced by bound GFP and NLPs. The validity of the thermodynamic model was confirmed when it was found that the statistical mixing distribution as a function of crowding energy for smaller GFP and larger NLPs collapsed to the same trend line for each GUV composition. Moreover, results of this analysis show that the free energy of mixing for a ternary lipid bilayer consisting of DOPC, DPPC, and cholesterol varied from 7.9 × 10 –22 to 1.5 × 10 –20 J/lipid at the compositions observed, decreasing as the relative cholesterol concentration was increased. It was discovered that there appears to be a maximum packing density, and associated maximum crowding pressure, of the NLPs, suggestive of circular packing. A similarity in mixing induced by NLP1 and NLP3 despite large difference in projected areas was analytically consistent with monovalent (one histidine tag) versus divalent (two histidine tags) surface interactions, respectively. In addition to GUVs, binding and induced mixing behavior of NLPs was also observed on planar, supported lipid multibilayers. Furthermore, the mixing process was reversible, with Lo domains reappearing after addition of EDTA for NLP removal.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2014

Coupled diffusion in lipid bilayers upon close approach

Biomembrane interfaces create regions of slowed water dynamics in their vicinity. When two lipid bilayers come together, this effect is further accentuated, and the associated slowdown can affect the dynamics of larger-scale processes such as membrane fusion. We have used molecular dynamics simulations to examine how lipid and water dynamics are affected as two lipid bilayers approach each other. These two interacting fluid systems, lipid and water, both slow and become coupled when the lipid membranes are separated by a thin water layer. We show in particular that the water dynamics become glassy, and diffusion of lipids in the apposed leaflets becomes coupled across the water layer, while the “outer” leaflets remain unaffected. This dynamic coupling between bilayers appears mediated by lipid–water–lipid hydrogen bonding, as it occurs at bilayer separations where water–lipid hydrogen bonds become more common than water–water hydrogen bonds. We further show that such coupling occurs in simulations of vesicle–vesicle fusion prior to the fusion event itself. As a result, such altered dynamics at membrane–membrane interfaces may both stabilize the interfacial contact and slow fusion stalk formation within the interface region.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2024

(2 + δ)-dimensional theory of the electromechanics of lipid membranes: Electrostatics

The coupling of electric fields to the mechanics of lipid membranes gives rise to intriguing electromechanical behavior, as, for example, evidenced by the deformation of lipid vesicles in external electric fields. Electromechanical effects are relevant for many biological processes, such as the propagation of action potentials in axons and the activation of mechanically gated ion channels. Currently, a theoretical framework describing the electromechanical behavior of arbitrarily curved and deforming lipid membranes does not exist. Purely mechanical models commonly treat lipid membranes as two-dimensional surfaces, ignoring their finite thickness. While holding analytical and numerical merit, this approach cannot describe the coupling of lipid membranes to electric fields and is thus unsuitable for electromechanical models. In a sequence of articles, we derive an effective surface theory of the electromechanics of lipid membranes, called the (2 + δ)-dimensional theory, which has the advantages of surface descriptions while accounting for finite thickness effects. The present article proposes a generic dimension reduction procedure relying on low-order spectral expansions. This procedure is applied to the electrostatics of lipid membranes to obtain the (2 + δ)-dimensional theory that captures potential differences across and electric fields within lipid membranes. Finally, this model is tested on different geometries relevant for lipid membranes, showing good agreement with the corresponding three-dimensional electrostatics theory.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗