Individual Lipid Molecules Research Articles

Nonequilibrium Molecular Dynamics Method to Generate Poiseuille-Like Flow between Lipid Bilayers.

There are various flows inside and outside cells in vivo. Nonequilibrium molecular dynamics (NEMD) simulation is a useful tool for understanding the effects of these flows on the dynamics of biomolecules. We propose an NEMD method to generate a Poiseuille-like flow between lipid bilayers. We extended the conventional equilibrium MD method to produce a flow by adding constant external force terms to the water molecules. Using the Lagrange multiplier method, the center of mass of the lipid bilayer is constrained so that the flow does not sweep away the lipid bilayer, but the individual lipid molecules fluctuate. The temperature of the system is controlled properly in the solution and membrane by using the Nosé-Hoover thermostat. We found that the flow velocity increases linearly as the applied external force term increases. It is possible to estimate the appropriate value of acceleration to generate a flow with an arbitrary velocity using this proportional relation once a single short MD simulation is performed. We also found that the flow between two lipid bilayers is slower than the analytical solution of the Navier-Stokes equations between rigid parallel plates due to the interactions between water molecules and the membrane. This method can be applied not only to a flow on lipid membranes but also to a flow on soft surfaces generally.

Lipid-mediated adaptation of proteins and peptides in cell membranes

The paper overviews the results of computational studies of the molecular mechanisms underlying the adaptation of model cell membranes taking place during their interaction with proteins and peptides. We discuss changes in the structural and dynamic parameters of the water–lipid environment, the hydrophobic/hydrophilic organization of the lipid bilayer surface (the so-called “mosaicity”), etc. Taken together, these effects are called the “membrane response” (MR) and constitute the most important ability of the cell membranes to respond specifically and consistently to the incorporation of extraneous agents, primarily proteins and peptides, and their subsequent functioning. The results of the authors’ long-term research in the field of molecular modeling of MR processes with various spatial and temporal characteristics are described, from the effects of binding of individual lipid molecules to proteins to changes in the integral macroscopic parameters of membranes. The bulk of the results were obtained using the “dynamic molecular portrait” approach developed by the authors. The biological role of the observed phenomena and potential ways of rationally designing artificial membrane systems with specified MR characteristics are discussed. This, in turn, is important for targeted changes in the activity profile of proteins and peptides exerting action on biomembranes, not least as promising pharmacological agents.

Generation of a Nonbilayer Lipid Nanoenvironment after Epitope Binding Potentiates Neutralizing HIV-1 MPER Antibody.

Establishment of interactions with the envelope lipids is a cardinal feature of broadly neutralizing antibodies (bnAbs) that recognize the Env membrane-proximal external region (MPER) of HIV. The lipid envelope constitutes a relevant component of the full "quinary" MPER epitope, and thus antibodies may be optimized through engineering their capacity to interact with lipids. However, the role of the chemically complex lipid nanoenvironment in the mechanism of MPER molecular recognition and viral neutralization remains poorly understood. To approach this issue, we computationally and experimentally investigated lipid interactions of broadly neutralizing antibody 10E8 and optimized versions engineered to enhance their epitope and membrane affinity by grafting bulky aromatic compounds. Our data revealed a correlation between neutralization potency and the establishment of favorable interactions with small headgroup lipids cholesterol and phosphatidylethanolamine, evolving after specific engagement with MPER. Molecular dynamics simulations of chemically modified Fabs in complex with an MPER-Transmembrane Domain helix supported the generation of a nanoenvironment causing localized deformation of the thick, rigid viral membrane and identified sphingomyelin preferentially occupying a phospholipid-binding site of 10E8. Together, these interactions appear to facilitate insertion of the Fabs through their engagement with the MPER epitope. These findings implicate individual lipid molecules in the neutralization function of MPER bnAbs, validate targeted chemical modification as a method to optimize MPER antibodies, and suggest pathways for MPER peptide-liposome vaccine development.

Mass Spectrometry Imaging Reveals Region-Specific Lipid Alterations in the Mouse Brain in Response to Efavirenz Treatment.

Efavirenz (EFV) is a commonly used drug to treat human immunodeficiency virus infection and is known to exert adverse effects on the brain. Although it is known that EFV is associated with abnormal plasma lipid levels, the changes in the spatial localization of individual lipid molecules in brain tissue following EFV treatment are yet to be explored. In this study, we employed a matrix-assisted laser desorption/ionization mass spectrometry imaging approach to determine region-specific lipid alterations in mouse brains following EFV treatment. We detected unique spatial localization patterns of phosphatidylcholine (PC), sphingomyelin (SM), ceramide phosphoinositol (PI-Cer), and hexosylceramide (HexCer) molecules in the mouse brain. Interestingly, PC(32:0), PC(38:5), and SM(36:1;O2) showed high abundance in the hippocampus region, whereas PI-Cer(38:8) exhibited low abundance in the hippocampus region of the EFV-treated mouse brains. Additionally, we observed low abundance of PC(38:6), PC(40:6), and PI-Cer(40:3) in the thalamus region of the EFV-treated mouse brains. Furthermore, SM(40:1;O2), SM(42:2;O2), SM(42:1;O2), SM(43:2;O2), and SM(43:1;O2) exhibited their accumulation in the corpus callosum region of the EFV-treated mouse brains as compared to controls. However, HexCer(42:1;O3) exhibited depletion in the corpus callosum region in response to EFV treatment. To characterize the expression patterns of proteins, including lipid metabolizing enzymes, in response to EFV treatment, mass spectrometry-based proteomics was utilized. From these, the expression levels of 12 brain proteins were found to be significantly decreased following EFV treatment. Taken together, these multiomics data provide important insights into the effects of EFV on brain lipid metabolism.

Enzyme Related Synthesis of Lipids and Fabrication of Planar Lipid Membranes

Biological membranes are structurally and functionally complex supramolecular assemblies. The intricate complexity itself poses a significant barrier in investigating the constituents, components, and their structure-activity relationships. Scientists employ twosynthetic methods to reduce complexity: the top-down approach and the bottom-up approach. The top-down synthetic approach involves genome reduction of the living cell, leading to a collateral reduction in membrane complexity. In contrast, the bottom-upsynthetic approach like chemical and enzymatic synthesis engages assembly of non-living components to construct biomimetic membrane structures with desired complexity. The synthetic routes catalyzed by enzymes are referred to as enzymatic synthesis, while routes utilizing a combination of catalytic systems and enzymes are known as chemo-enzymatic synthesis. The lipids prepared by enzymatic or chemo-enzymatic method are essential to integrate into a membrane in a manner that makes them amenable to various analytical techniques. Planar lipid bilayer method is one such versatile technique which can be used to prepare membranes from individual lipid molecules to utilize in various analytical procedures. Two planar lipid membranes types, black lipid membrane and supported lipid membrane, are more common than other types due to their less complexity in preparation. This review discusses the enzyme related synthesis of lipids, the method of preparation and challenges involved in fabricating black lipid membrane and supported lipid membrane models.

Lateral Transport of Domains in Anionic Lipid Bilayer Membranes under DC Electric Fields: A Coarse-Grained Molecular Dynamics Study.

Dynamic lateral transport of lipids, proteins, and self-assembled structures in biomembranes plays a crucial role in diverse cellular processes. In this study, we perform coarse-grained molecular dynamics simulations on a vesicle composed of a binary mixture of neutral and anionic lipids to investigate the lateral transport of individual lipid molecules and the self-assembled lipid domains upon an applied direct current (DC) electric field. Under the potential force of the electric field, a phase-separated domain rich in anionic lipids is trapped in the opposite direction of the electric field. The subsequent reversal of the electric field induces unidirectional domain motion. During the domain motion, the domain size remains constant, but a considerable amount of the anionic lipids is exchanged between the anionic-lipid-rich domain and the surrounding bulk. While the speed of the domain motion (collective lipid motion) shows a significant positive correlation with the electric field strength, the exchange of anionic lipids between the domain and bulk (individual lipid motion) exhibits no clear correlation with the field strength. The mean velocity field of the lipids surrounding the domain displays a two-dimensional (2D) source dipole. We revealed that the balance between the potential force of the applied electric field and the quasi-2D hydrodynamic frictional force well explains the dependence of the domain motions on the electric field strengths. The present results provide insight into the hierarchical dynamic responses of self-assembled lipid domains to the applied electric field and contribute to controlling the lateral transportation of lipids and membrane inclusions.

Analysis of Phase Heterogeneity in Lipid Membranes Using Single-Molecule Tracking in Live Cells.

In live cells, the plasma membrane is composed of lipid domains separated by hundreds of nanometers in dynamic equilibrium. Lipid phase separation regulates the trafficking and spatiotemporal organization of membrane molecules that promote signal transduction. However, visualizing domains with adequate spatiotemporal accuracy remains challenging because of their subdiffraction limit size and highly dynamic properties. Here, we present a single lipid-molecular motion analysis pipeline (lipid-MAP) for analyzing the phase heterogeneity of lipid membranes by detecting the instantaneous velocity change of a single lipid molecule using the excellent optical properties of nanoparticles, high spatial localization accuracy of single-molecule localization microscopy, and separation capability of the diffusion state of the hidden Markov model algorithm. Using lipid-MAP, individual lipid molecules were found to be in dynamic equilibrium between two statistically distinguishable phases, leading to the formation of small (∼170 nm), viscous (2.5× more viscous than surrounding areas), and transient domains in live cells. Moreover, our findings provide an understanding of how membrane compositional changes, i.e., cholesterol and phospholipids, affect domain formation. This imaging method can contribute to an improved understanding of spatiotemporal-controlled membrane dynamics at the molecular level.

Metabolomic analysis of lipid changes in Bombyx mori infected with Nosema bombycis

The silkworm (Bombyx mori) is a model species of lepidopteran insect. Microsporidium spp. are obligate intracellular eukaryotic parasites. Infection by the microsporidian Nosema bombycis (Nb) results in an outbreak of Pébrine disease in silkworms and causes substantial losses to the sericulture industry. It has been suggested that Nb depends on nutrients from host cells for spore growth. However, little is known about changes in lipid levels after Nb infection. In this study, ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was performed to analyze the effect of Nb infection on lipid metabolism in the midgut of silkworms. A total of 1601 individual lipid molecules were detected in the midgut of silkworms, of which 15 were significantly decreased after Nb challenge. Classification, chain length, and chain saturation analysis revealed that these 15 differential lipids can be classified into different lipid subclasses, of which 13 belong to glycerol phospholipid lipids and two belong to glyceride esters. The results indicated that Nb uses the host lipids to complete its own replication, and the acquisition of host lipid subclasses is selective; not all lipid subclasses are required for microsporidium growth or proliferation. Based on lipid metabolism data, phosphatidylcholine (PC) was found to be an important nutrient for Nb replication. Diet supplementation with lecithin substantially promoted the replication of Nb. Knockdown and overexpression of the key enzyme phosphatidate phosphatase (PAP) and phosphatidylcholine (Bbc) for PC synthesis also confirmed that PC is necessary for Nb replication. Our results showed that most lipids in the host midgut decreased when silkworms were infected with Nb. Reduction of or supplementation with PC may be a strategy to suppress or promote microsporidial replication.

Revealing Sex and Alzheimer’s Disease‐related Changes in the Spatial Localization of Brain Lipids in Mice using Mass Spectrometry Imaging

Lipids are essential biomolecules in the brain, as they have important roles in signaling and structural integrity. Of note, the central nervous system has a high concentration of lipids, second only to adipose tissue. Recently, it has been shown that abnormalities in lipid levels play a critical role in the onset of neurodegenerative diseases including Alzheimer’s disease (AD). AD is a progressive and severe neurodegenerative disease and the leading cause for dementia, affecting millions worldwide. However, the spatial localization of individual lipid molecules in normal brain tissues, as well as region‐specific lipid alterations during AD are yet to be explored. Additionally, current understanding of potential sexual dimorphisms in lipid localization in brain is incomplete. With these in mind, we employed high‐resolution matrix‐assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) coupled to ion mobility mass spectrometry to characterize region‐specific lipid distribution in brain obtained from age‐ and sex‐matched wild type and AD mice (18‐month‐old female C57BL/6J and 3xTg‐AD mice, which exhibits both amyloid and tau pathology, n=3 per group). Additionally, the spatial distributions of lipids were investigated in male and female mice within two different age groups (4 and 12‐week‐old, n=3 per group). From these experiments, we were able to detect more than one thousand ions in brain tissue sections. Following detection, we annotated an approximate 100 lipid molecules with high confidence. Tissue imaging results revealed region‐specific distributions of specific lipids representing a range of classes including phosphatidylcholines, lysophosphatidylcholines, phosphatidylethanolamines, ceramide phosphates, sphingomyelins, sulfated hexosyl ceramides, and ceramide phosphoinositols across male and female mice. Interestingly, ceramide phosphate (30:7), lysophosphatidylcholine (16:0), and phosphatidylcholine (36:5) molecules exhibited sex‐specific localization patterns restricted to the cerebellum in 4‐week‐old male mice. Further, ceramide phosphoinositol (42:6) was localized to the cerebellum region of 12‐week‐old male and female mice whereas 4‐week‐old male and female mice showed relative homogeneous spatial distribution. Notably, we observed region‐specific alterations in the spatial localization of several lipid molecules including phosphatidylcholine [(40:6), and (40:7)] and sulfated hexosyl ceramide [(16:1;2O/22:2;O), (24:2;2O/12:1;O), and (19:0;2O/15:0;O)] in AD mice as compared to age‐ and sex‐matched controls. These observed changes occurred in the hippocampus region and were further confirmed using receiver operating characteristic analysis. Taken together, the above results reveal highly localized patterns of alterations in lipid molecules across male and female mice, as well as during AD.

Molecular dynamics simulations and solid-state nuclear magnetic resonance spectroscopy measurements of C-H bond order parameters and effective correlation times in a POPC-GM3 bilayer.

Glycolipids such as gangliosides affect the properties of lipid membranes and in extension the interactions between membranes and other biomolecules like proteins. To better understand how the properties of individual lipid molecules can contribute to shape the functional aspects of a membrane, the spatial restriction and dynamics of C-H bond segments can be measured using nuclear magnetic resonance (NMR) spectroscopy. We combine solid-state NMR spectroscopy with all-atom molecular dynamics (MD) simulations to investigate how ganglioside GM3 affects the bilayer structure and dynamics of C-H bond segments. These two methods yield reorientational correlation functions, molecular profiles of C-H bond order parameters |SCH| and effective correlation times τe, which we compare for lipids in POPC bilayers with and without 30 mol% GM3. Our results revealed that all C-H segments of POPC reorient slower in the presence of GM3 and that the defining features of the GM3-POPC bilayer lie in the GM3 headgroup; it gives the bilayer an extended headgroup layer with high order (|SCH| up to 0.3-0.4) and slow dynamics (τe up to 100 ns), a character that may be mechanistically important in ganglioside interactions with other biomolecules.

Mouse lipidomics reveals inherent flexibility of a mammalian lipidome

Lipidomics has become an indispensable method for the quantitative assessment of lipid metabolism in basic, clinical, and pharmaceutical research. It allows for the generation of information-dense datasets in a large variety of experimental setups and model organisms. Previous studies, mostly conducted in mice (Mus musculus), have shown a remarkable specificity of the lipid compositions of different cell types, tissues, and organs. However, a systematic analysis of the overall variation of the mouse lipidome is lacking. To fill this gap, in the present study, the effect of diet, sex, and genotype on the lipidomes of mouse tissues, organs, and bodily fluids has been investigated. Baseline quantitative lipidomes consisting of 796 individual lipid molecules belonging to 24 lipid classes are provided for 10 different sample types. Furthermore, the susceptibility of lipidomes to the tested parameters is assessed, providing insights into the organ-specific lipidomic plasticity and flexibility. This dataset provides a valuable resource for basic and pharmaceutical researchers working with murine models and complements existing proteomic and transcriptomic datasets. It will inform experimental design and facilitate interpretation of lipidomic datasets.

A panel of blood lipids associated with cognitive performance, brain atrophy and diagnosis: A longitudinal study of elders without dementia

AbstractBackgroundBlood metabolites have been suggested as promising biomarkers of Alzheimer’s disease. Identifying diagnostic and predictive lipids can provide new spots in worse cognitive decline fields.MethodTotal 579 plasma lipid signatures were sampled in 374 participants without dementia at baseline enrolled in the Alzheimer’s Disease Neuroimaging Initiative cohort over 10 years. Ten‐fold cross‐validated least absolute shrinkage and selection operator‐logistic regression selected a subset of lipids that best classified individuals with worse slopes of cognitive decline determined by linear mixed models. Multivariable adjusted model examined associations between lipids and neuropsychiatric assessments, CSF biomarkers, brain structural measures and diagnostic categories.ResultIn a training and a validation set, a panel of seventeen lipids classified cognitively declined individuals with favorable prediction (training set: area under curve [AUC]=0.768, 95% confidence interval [CI]=0.715‐0.821; validation set: AUC =0.747, 95%CI= 0.627‐0.867) and calibration efficacy (Hosmer‐Lemeshow test: p>0.05). Adding risk score to the predictive model yielded a better AUC of 0.779 (95%CI=0.712‐0.845) than the one with clinical variables alone (p=0.014). The model combining polygenic hazard score, lipid signature and clinical variables yielded the best improvement in prediction. Baseline lipid signatures consisting of all selected lipids independently predicted declined cognition and positively associated with baseline cognitive performance (p=0.007) and cerebrospinal tau protein changes (p‐tau, p=0.025; t‐tau, p=0.010). Longitudinal analyses showed lipid signatures had adverse impacts on cognitive performance and brain atrophy over 10 years, and predicted diverse diagnostic categories (case vs. control, stable mild cognitive impairment [MCI] vs. cognitively normal [CN], progressive MCI vs.CN, A+[positive β‐amyloid deposition] vs. A‐[negative β‐amyloid deposition] , A+T+ [positive tau pathology] vs. A‐T‐[negative tau pathology]) and a trend for progressive outcomes.ConclusionA comprehensive panel of peripheral lipids instead of individual lipid molecule could better diagnose and predict cognitive decline. Further, integrating genetic variations, proteins and other biological information in future may expand the fit of exited detect models.

Recent advances in analytical strategies for mass spectrometry-based lipidomics

Lipids are vital biological molecules and play multiple roles in cellular function of mammalian organisms such as cellular membrane anchoring, signal transduction, material trafficking and energy storage. Driven by the biological significance of lipids, lipidomics has become an emerging science in the field of omics. Lipidome in biological systems consists of hundreds of thousands of individual lipid molecules that possess complex structures, multiple categories, and diverse physicochemical properties assembled by different combinations of polar headgroups and hydrophobic fatty acyl chains. Such structural complexity poses a huge challenge for comprehensive lipidome analysis. Thanks to the great innovations in chromatographic separation techniques and the continuous advances in mass spectrometric detection tools, analytical strategies for lipidomics have been highly diversified so that the depth and breadth of lipidomics have been greatly enhanced. This review will present the current state of mass spectrometry-based analytical strategies including untargeted, targeted and pseudotargeted lipidomics. Recent typical applications of lipidomics in biomarker discovery, pathogenic mechanism and therapeutic strategy are summarized, and the challenges facing to the field of lipidomics are also discussed.

Out-of-Plane Nanoscale Reorganization of Lipid Molecules and Nanoparticles Revealed by Plasmonic Spectroscopy.

Lipid bilayers assembled on solid substrates have been extensively studied with single-molecule resolution as the constituent molecules diffuse in 2D; however, the out-of-plane motion is typically ignored. Here we present the subnanometer out-of-plane diffusion of nanoparticles attached to hybrid lipid bilayers (HBLs) assembled on metal surfaces. The nanoscale cavity formed between the Au nanoparticle and Au film provides strongly enhanced optical fields capable of locally probing HBLs assembled in the gaps. This allows us to spectroscopically resolve the nanoparticles assembled on bilayers, near edges, and in membrane defects, showing the strong influence of charged lipid rafts. Nanoparticles sitting on the edges of the HBL are observed to flip onto and off of the bilayer, with flip energies of ∼10 meV showing how thermal energies dynamically modify lipid arrangements around a nanoparticle. We further resolve the movement of individual lipid molecules by doping the HBL with low concentrations of Texas Red (TxR) dye-labeled lipids.

Principal component analysis highlights the influence of temperature, curvature and cholesterol on conformational dynamics of lipids

Membrane lipids are inherently highly dynamic molecules. Currently, it is difficult to probe the structures of individual lipids experimentally at the timescales corresponding to atomic motions, and consequently molecular dynamics simulations are used widely. In our previous work, we have introduced the principal component analysis (PCA) as a convenient framework for comprehensive quantitative description of lipid motions. Here, we present a newly developed open source script, PCAlipids, which automates the analysis and allows us to refine the approach and test its limitations. We use PCAlipids to determine the influence of temperature, cholesterol and curvature on individual lipids, and show that the most prominent lipid tail scissoring motion is strongly affected by these factors and allows tracking of phase transition. Addition of cholesterol affects the conformations and selectively changes the dynamics of lipid molecules, impacting the large-amplitude motions. Introduction of curvature biases the conformational ensembles towards more extended structures. We hope that the developed approach will be useful for understanding the molecular basis of different processes occurring in lipid membrane systems and will stimulate development of complementary experimental techniques probing the conformations of individual lipid molecules.

Quasi-Atomistic Approach to Modeling of Liposomes

Small-angle X-ray scattering is an important structural tool for studying biological membranes; however, interpretation of scattering data remains a challenging problem. In most cases, analysis makes it possible to determine some structural parameters and the electron density profile of lipid bilayers, but no methods providing more detailed information (e.g., about the structural organization of vesicles) have been proposed yet. An approach making it possible to determine the main integral characteristics of liposomes using small-angle scattering is presented in this study. Within this approach a quasi-atomic model of liposome is built from individual lipid molecules, which form a sphere or a hollow ellipsoid. The method has been implemented in a computer program, verified on experimental small-angle X-ray scattering data, and proposed to analyze the structure of lipid vesicles and their interactions with proteins.

The Effect of Serotonin on the Lateral Segregation of a Raft Membrane Mixture

Lipids may laterally segregate in membranes, especially in the presence of cholesterol. In cells, a vast diversity of molecules, such as proteins, neurotransmitters, and hormones could also affect the lateral segregation of the individual lipid molecules. Serotonin is an important neurotransmitter for physiological brain function. Serotonin has several physiological membrane receptors but has recently been shown to also bind to membranes with high affinity. Consequently, serotonin could also affect the membranes through indirect interactions among lipids or by changing lipid-lipid interactions. In this study, we have used 2H NMR to characterise, the effect of serotonin on the lateral segregation in 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine(POPC)/Palmitoyl-sphingomyelin/cholesterol bilayers by deuterating the individual lipids species. In addition, we have studied the membrane distribution of serotonin in POPC bilayers using 1H NOESY NMR under magic-angle spinning conditions to understand the molecular details of serotonin-lipid interaction. We observed a clear effect of serotonin on phase separation as observed in the 2H NMR spectra of the the samples studied. In conclusion, serotonin influences lateral segregation that could be relevant for its physiological function. We will discuss the effect of serotonin on the individual lipid species studied.

Uncoupling between the lipid membrane dynamics of differing hierarchical levels.

Diverse biological functions of biomembranes are made possible by their rich dynamic behaviors across multiple scales. While the potential coupling between the dynamics of differing scales may underlie the machineries regulating the biomembrane-involving processes, the mechanism and even the existence of this coupling remain an open question, despite the latter being taken for granted. Via inelastic neutron scattering, we examined dynamics across multiple scales for the lipid membranes whose dynamic behaviors were perturbed by configurational changes at two membrane regions. Surprisingly, the dynamic behavior of individual lipid molecules and their collective motions were not always coupled. This suggests that the expected causal relation between the dynamics of the differing hierarchical levels does not exist and that an apparent coupling can emerge by manipulating certain membrane configurations. The findings provide insight on biomembrane modeling and how cells might individually or concertedly control the multiscale membrane dynamics to regulate their functions.

A panel of blood lipids associated with cognitive performance, brain atrophy, and Alzheimer's diagnosis: A longitudinal study of elders without dementia.

IntroductionWe sought lipid‐metabolic biomarkers involved in the processes underlying cognitive decline and detected them in association with Alzheimer's disease (AD) phenotypes.MethodsA least absolute shrinkage and selection operator logistic regression model was used to select lipids that best classified cognitive decline defined by a fast‐annual rate of cognition. Lipid summary scores were constructed as predictors of cognitive decline by using this model. Multivariable‐adjusted models tested the associations of risk score with AD phenotypes.ResultsA model incorporating 17 selected lipids showed good discrimination and calibration. The lipid risk score was positively associated with the baseline Alzheimer Disease Assessment Scale—13‐item cognitive subscale (ADAS‐Cog13) score and cerebrospinal tau protein level, and predicted cognitive diagnoses. Additional results showing that individuals with increased lipid risk scores had rapid change rates of ADAS‐Cog13 and brain atrophy further corroborated the predictive role of lipids.DiscussionA panel of blood lipids instead of individual lipid molecules could better diagnose and predict cognitive decline.

A machine learning study of the two states model for lipid bilayer phase transitions.

We have adapted a set of classification algorithms, also known as machine learning, to the identification of fluid and gel domains close to the main transition of dipalmitoyl-phosphatidylcholine (DPPC) bilayers. Using atomistic molecular dynamics conformations in the low and high temperature phases as learning sets, the algorithm was trained to categorise individual lipid configurations as fluid or gel, in relation with the usual two-states phenomenological description of the lipid melting transition. We demonstrate that our machine can learn and sort lipids according to their most likely state without prior assumption regarding the nature of the order parameter of the transition. Results from our machine learning study provide strong support in favour of a two-states model approach of membrane fluidity.