Lipid Domains Research Articles

Thermoplasmonic Vesicle Fusion Reveals Membrane Phase Segregation of Influenza Spike Proteins.

Many cellular processes involve the lateral organization of integral and peripheral membrane proteins into nanoscale domains. Despite the biological significance, the mechanisms that facilitate membrane protein clustering into nanoscale lipid domains remain enigmatic. In cells, the analysis of membrane protein phase affinity is complicated by the size and temporal nature of ordered and disordered lipid domains. To overcome these limitations, we developed a method for delivering membrane proteins from transfected cells into phase-separated model membranes that combines optical trapping with thermoplasmonic-mediated membrane fusion and confocal imaging. Using this approach, we observed clear phase partitioning into the liquid disordered phase following the transfer of GFP-tagged influenza hemagglutinin and neuraminidase from transfected cell membranes to giant unilamellar vesicles. The generic platform presented here allows investigation of the phase affinity of any plasma membrane protein which can be labeled or tagged with a fluorescent marker.

Sensitive and selective polymer condensation at membrane surface driven by positive co-operativity

Biomolecular phase separation has emerged as an essential mechanism for cellular organization. How cells respond to environmental stimuli in a robust and sensitive manner to build functional condensates at the proper time and location is only starting to be understood. Recently, lipid membranes have been recognized as an important regulatory center for biomolecular condensation. However, how the interplay between the phase behaviors of cellular membranes and surface biopolymers may contribute to the regulation of surface condensation remains to be elucidated. Using simulations and a mean-field theoretical model, we show that two key factors are the membrane's tendency to phase-separate and the surface polymer's ability to reorganize local membrane composition. Surface condensate forms with high sensitivity and selectivity in response to features of biopolymer when positive co-operativity is established between coupled growth of the condensate and local lipid domains. This effect relating the degree of membrane-surface polymer co-operativity and condensate property regulation is shown to be robust by different ways of tuning the co-operativity, such as varying membrane protein obstacle concentration, lipid composition, and the affinity between lipid and polymer. The general physical principle emerged from the current analysis may have implications in other biological processes and beyond.

CHARMM-GUI Membrane Builder: Past, Current, and Future Developments and Applications.

Molecular dynamics simulations of membranes and membrane proteins serve as computational microscopes, revealing coordinated events at the membrane interface. As G protein-coupled receptors, ion channels, transporters, and membrane-bound enzymes are important drug targets, understanding their drug binding and action mechanisms in a realistic membrane becomes critical. Advances in materials science and physical chemistry further demand an atomistic understanding of lipid domains and interactions between materials and membranes. Despite a wide range of membrane simulation studies, generating a complex membrane assembly remains challenging. Here, we review the capability of CHARMM-GUI Membrane Builder in the context of emerging research demands, as well as the application examples from the CHARMM-GUI user community, including membrane biophysics, membrane protein drug-binding and dynamics, protein-lipid interactions, and nano-bio interface. We also provide our perspective on future Membrane Builder development.

Tuning Targeted Liposome Avidity to Cells via Lipid Phase Separation.

The addition of both cell-targeting moieties and polyethylene glycol (PEG) to nanoparticle (NP) drug delivery systems is a standard approach to improve the biodistribution, specificity, and uptake of therapeutic cargo. The spatial presentation of these molecules affects avidity of the NP to target cells in part through an interplay between the local ligand concentration and the steric hindrance imposed by PEG molecules. Here, we show that lipid phase separation in nanoparticles can modulate liposome avidity by changing the proximity of PEG and targeting protein molecules on a nanoparticle surface. Using lipid-anchored nickel-nitrilotriacetic acid (Ni-NTA) as a model ligand, we demonstrate that the attachment of lipid anchored Ni-NTA and PEG molecules to distinct lipid domains in nanoparticles can enhance liposome binding to cancer cells by increasing ligand clustering and reducing steric hindrance. We then use this technique to enhance the binding of RGD-modified liposomes, which can bind to integrins overexpressed on many cancer cells. These results demonstrate the potential of lipid phase separation to modulate the spatial presentation of targeting and shielding molecules on lipid nanocarriers, offering a powerful tool to enhance the efficacy of NP drug delivery systems.

Lipid domain boundary triggers membrane damage and protein folding of human islet amyloid polypeptide in the early pathogenesis of amyloid diseases

The misfolding and self-aggregation of human Islet Amyloid Polypeptide (hIAPP) are linked to the onset of type 2 diabetes (T2D). However, the mechanism of how the disordered hIAPP aggregates trigger membrane damage leading to the loss of Islet cells in T2D is unknown. Using coarse-grained (CG) and all-atom (AA) molecular dynamics simulations, we have investigated the membrane-disruption behaviors of hIAPP oligomers on the phase-separated lipid nanodomains that mimic the highly heterogeneous lipid raft structures of cell membranes. Our results revealed that hIAPP oligomers preferentially bind to the liquid-ordered and liquid-disordered domain boundary around two hydrophobic residues at L16 and I26, and lipid acyl chain order disruption and beta-sheet formation occur upon hIAPP binding to the membrane surface. We propose that the lipid order disruption and surface-induced beta-sheet formation on the lipid domain boundary represent the early molecular events of membrane damage associated with the early pathogenesis of T2D.

Cholesterol Regulation of Membrane Proteins Revealed by Two-Color Super-Resolution Imaging.

Cholesterol and phosphatidyl inositol 4,5-bisphosphate (PIP2) are hydrophobic molecules that regulate protein function in the plasma membrane of all cells. In this review, we discuss how changes in cholesterol concentration cause nanoscopic (<200 nm) movements of membrane proteins to regulate their function. Cholesterol is known to cluster many membrane proteins (often palmitoylated proteins) with long-chain saturated lipids. Although PIP2 is better known for gating ion channels, in this review, we will discuss a second independent function as a regulator of nanoscopic protein movement that opposes cholesterol clustering. The understanding of the movement of proteins between nanoscopic lipid domains emerged largely through the recent advent of super-resolution imaging and the establishment of two-color techniques to label lipids separate from proteins. We discuss the labeling techniques for imaging, their strengths and weakness, and how they are used to reveal novel mechanisms for an ion channel, transporter, and enzyme function. Among the mechanisms, we describe substrate and ligand presentation and their ability to activate enzymes, gate channels, and transporters rapidly and potently. Finally, we define cholesterol-regulated proteins (CRP) and discuss the role of PIP2 in opposing the regulation of cholesterol, as seen through super-resolution imaging.

Paraoxonase 1 and atherosclerosis.

Paraoxonase 1 (PON1), residing almost exclusively on HDL, was discovered because of its hydrolytic activity towards organophosphates. Subsequently, it was also found to hydrolyse a wide range of substrates, including lactones and lipid hydroperoxides. PON1 is critical for the capacity of HDL to protect LDL and outer cell membranes against harmful oxidative modification, but this activity depends on its location within the hydrophobic lipid domains of HDL. It does not prevent conjugated diene formation, but directs lipid peroxidation products derived from these to become harmless carboxylic acids rather than aldehydes which might adduct to apolipoprotein B. Serum PON1 is inversely related to the incidence of new atherosclerotic cardiovascular disease (ASCVD) events, particularly in diabetes and established ASCVD. Its serum activity is frequently discordant with that of HDL cholesterol. PON1 activity is diminished in dyslipidaemia, diabetes, and inflammatory disease. Polymorphisms, most notably Q192R, can affect activity towards some substrates, but not towards phenyl acetate. Gene ablation or over-expression of human PON1 in rodent models is associated with increased and decreased atherosclerosis susceptibility respectively. PON1 antioxidant activity is enhanced by apolipoprotein AI and lecithin:cholesterol acyl transferase and diminished by apolipoprotein AII, serum amyloid A, and myeloperoxidase. PON1 loses this activity when separated from its lipid environment. Information about its structure has been obtained from water soluble mutants created by directed evolution. Such recombinant PON1 may, however, lose the capacity to hydrolyse non-polar substrates. Whilst nutrition and pre-existing lipid modifying drugs can influence PON1 activity there is a cogent need for more specific PON1-raising medication to be developed.

Cholesterol affects voltage-gated proton channels indirectly.

A number of membrane proteins, including ion channels, interact directly with cholesterol within the plasma membrane. This interaction may affect physiologically relevant properties of the protein. Often, protein-sterol interaction is facilitated by a cholesterol recognition amino acid consensus sequence (CRAC) domain with (L/V)-X1-5-(Y)-X1-5-(K/R) or the inverse sequence CARC (K/R)-X1-5-(Y/F)-X1-5-(L/V) (Fantini & Barrantes, 2013, Front. Physiol. 4:31). The human proton channel hHV1 contains a putative CARC sequence KNNYAAMV (amino-acid residues 131-138) within the extrafacial part of its S2 transmembrane domain. We explored effects of cholesterol depletion from or addition to the membrane. Modulation of cholesterol levels using methyl-β-cyclodextrin (MBCD) dramatically altered current amplitude in inside-out membrane patches. Mutations to the CARC domain did not alter the effects of cholesterol, indicating that cholesterol binding to the CARC domain is not responsible. We propose that hHV1 molecules preferentially associate with cholesterol-dependent domains within the membrane. Cholesterol might affect proton currents if varying cholesterol changes the distribution of hHV1 molecules in the membrane between the cholesterol-dependent lipid domains and the rest of the membrane. A previous study reported that suction increased proton currents in excised patches and this was interpreted as evidence for mechanosensitivity of the HV1 protein (Pathak et al, 2016, J. Gen. Physiol. 148:405). We have confirmed that suction applied to the pipette increases proton currents. This observation is consistent with our hypothesis since membrane tension will undoubtedly affect the association of individual Hv1 molecules with lipid domains without the need for bona fide channel mechanosensitivity. Increase in membrane tension would result in the increased proton currents due to the dispersal of condensed lipid domains in a similar way to the cholesterol depletion. This study provides the first indication that HV1 associates with membrane lipid domains, sometimes called lipid rafts.

Lipid-mediated interplay between host restriction factor Serinc5 and HIV-1 ENV glycoprotein.

Human immunodeficiency virus (HIV-1) is a pathogenic retrovirus that continues to be a severe threat to public health. HIV-1 is an enveloped virus that enters and infects cells through cell-virus membrane fusion, mediated by HIV-1 envelope glycoprotein, Env.The host restriction factor, Serinc5, impairs this process. It reduces HIV infection rates by incorporating itself into the viral membrane and blocking fusion of the virus with the plasma membrane of uninfected cells. The exact restriction mechanism of Serinc5 remains unknown. Studies suggest that Serinc5 disrupts Env distribution at the membrane and inhibits the protein's fusion function. We hypothesize that Serinc5 acts on Env by altering the physical properties of the surrounding membrane. In this study, we evaluate the nature of the membrane properties affected by Serinc5. Applying the fluorescent probe FLIPPER-TR to measure membrane order in viral particles with and without Serinc5, we discovered that Serinc5 slightly increases lipid order. HIV-1 bearing Env with a truncated cytoplasmic tail (∆CT) avoids infection restriction by Serinc5. We used isolated giant plasma membrane vesicles (GPMVs) to quantify Serinc5 and Env partitioning into specific lipid domains. Our results indicate that Serinc5 and Env partition into the liquid-disordered lipid domains of the plasma membrane. Interestingly, mutant Env ∆CT showed different lipid phase preferences than Serinc5 and wild-type Env. We discuss how these different lipid interactions might affect entry of progeny viruses into cells by membrane fusion.

Experimental and computational study of membrane permeabilization and translocation of the dynorphin A neuropeptide.

Dynorphins are endogenous neuropeptides that function as ligands for the κ-opioid receptor. In addition to opioid activity, dynorphins can induce several pathological effects such as neurological dysfunctions and cell death. Previous studies have suggested that Dynorphin A (DynA) mediates some pathogenic actions through formation of transient pores in lipid domains or translocation across the plasma membrane. Here, we use planar bilayer electrophysiology to show that DynA induces pore formation in negatively charged membranes. We find a large variability in pore conformations showing equilibrium conductance fluctuations, what disregards electroporation as the dominant mechanism of pore formation. Ion selectivity measurements showing cationic selectivity indicate that positive protein charges of DynA are stabilized by phosphatidyl serine negative charges in the formation of combined structures. We complement this study with computational simulations that assess the stability of diverse peptide arrangements in the hydrophobic core of the bilayer. We show that DynA is capable of assembling in charged membranes to form water-filled pores that conduct ions. Furthermore, we find that DynA generates membrane permeabilization events compatible with a translocation of the protein across the planar bilayer when using a neutral lipid. In these conditions, DynA is still capable of forming water-filled pores similar to those in a charged membrane, but translocation seems to be favored.

Lateral compression of lipids drives transbilayer coupling of protein condensates.

Protein phase separation that is restricted to a two-dimensional lipid membrane has recently gained much attention due to its involvement in various cellular processes. Two popular in vitro model membrane systems, giant unilamellar vesicles (GUVs) and supported lipid bilayers (SLBs), have been used to study it. However, due to the accessibility to only one side of the membrane in these systems, protein phase separation on both sides of the membrane remains unexplored. Here, we introduce a freestanding planar lipid membrane array as an effective platform to study membrane-associated protein phase separation. Protein condensates on the membrane display liquid-like features, and environmental stimuli, such as salt concentration and temperature, effectively control the observed phase separation results in our system with the application of several intrinsically disordered proteins. Interestingly, we observe transbilayer coupling of protein condensates such that protein-rich domains on one side of the membrane are found to colocalize with those on the other side of the membrane. How do these protein phases communicate across the lipid bilayer? Based on data from lipid probe partitioning and photobleaching experiments, we hypothesize that protein condensation on the membrane exerts lateral compressive stress on the underlying lipids, driving the formation of lipid domains with reduced fluidity. Specifically, lipid domains with reduced fluidity and increased lipid packing, formed by protein condensation on each membrane leaflet, are attracted to one another, leading to transbilayer coupling of protein condensates. These findings suggest a previously unknown mechanism by which cellular signals from one membrane leaflet, triggered by membrane-associated protein phase separation, can be transferred to the opposing leaflet.

Applying machine learning to investigate lipid domain formation behaviors in the presence of amyloidogenic proteins.

Cell membranes are not homogeneous but contain lipid nanodomains distributed on both leaflets of the lipid bilayers. Using microsecond molecular dynamics (MD) simulations, we have simulated phase-separated lipid bilayers (raft membranes) containing lipid nanodomains that mimic the heterogeneous structures of neuronal plasma membranes. Our recent studies indicate that these lipid nanodomains, e.g., the mixed liquid-ordered (Lo) and liquid-disordered (Ld) boundaries or Lod and ganglioside-cluster, represent non-specific and specific membrane damage targets of amyloidogenic protein, e.g., tau, aggregates (oligomers), in raft membranes. However, a robust computational tool to classify lipids into these lipid nanodomains and quantitate the spatial and temporal evolutions of the domain structures in the presence of amyloidogenic oligomers is not available. In this study, we have modified two unsupervised Machine Learning (ML) algorithms, Non-negative Matrix Factorization (NMFk) and K-Mean Clustering, to investigate lipid domain formation behaviors. These algorithms are currently used in mutation analysis of cancer genomes and feature extractions. In this work, NMFk was used to decompose our time-resolved lipid-lipid proximity data matrix into two latent “signature” and “activity” matrices, which contain a set of probability configurations and the time-dependent activity of those configurations, respectively, of the lipids participating in each nanodomain, e.g., Lo and Lod. On the other hand, by implementing additional spatial information to the dataset used in NMFk, the K-Mean Clustering sorts lipids into nanodomains and determines the latent temporal and spatial evolutions of each domain. Hence, by combining both ML algorithms, this study provides new insights into understanding protein-induced membrane damage mechanisms of amyloidogenic oligomers associated with lipid domain disruption behaviors that may contribute to the pathogenesis of Alzheimer's. (Supported by NSF [OAC 153159] and Welch Foundation [W-2057-2021-327].)

Domain-induced dynamics in phase-separating lipid membranes.

Lipid membranes have a significant role in cells, not only defining the boundaries of cells and cell organelles but also playing an active role in cell functions, including the partitioning of proteins and the spatiotemporal regulation of signaling clusters. This is facilitated by the rich lipid diversity in cell membranes, which often results in unideal mixing and subsequent lipid phase-separation into lateral compositional heterogeneities or domains. Over the past few decades, structural measurements on such membranes have shed important light on the molecular mechanisms underlying domain formation. However, major information gaps still exist in our understanding of how domain formation affects the dynamics of lipid membranes, whether in the form of collective fluctuations or molecular motions. To address this outstanding question, we use neutron spectroscopy and molecular dynamics (MD) simulations that can selectively investigate the matrix dynamics in domain-forming membranes. Specifically, our studies are performed on binary mixtures of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and deuterated 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC). Experimental results, obtained by neutron spin-echo spectroscopy and neutron backscattering spectroscopy, show that the formation and growth of rigid DSPC domains causes an effective slowdown in the bending fluctuations and diffusional dynamics of the otherwise fluid DMPC matrix. MD simulations on cognate bilayers suggest that the measured changes in the matrix dynamics are mediated by interfacial DMPC lipids that experience constrained diffusional jumps and longer residence times at the domain boundaries. Our findings present striking evidence of dynamic coupling between lipid domains and their surrounding lipid environment. More importantly, this interplay occurs on the nanosecond time scales of protein conformational changes and signaling events. Put together, the results suggest an intriguing mechanism by which domain formation can play a regulatory role in functional membrane processes.

Mutual regulation between coupled protein condensates and ordered membrane domains.

Downstream of T-cell receptor ligation, biomolecular condensates are produced via the multivalent binding between Linker for Activation of T-cells (LAT) and its effectors (Grb2 and Sos1) to facilitate T-cell activation. LAT is a transmembrane protein known to be recruited to ordered lipid domains, suggesting potential coupling between protein cytoplasmic condensates and lateral lipid-based phase-separation and organization. We report evidence demonstrating thermodynamic coupling between lipid- and protein-based phase separation. In model membranes, condensates formed on phase-separating membranes template ordered lipid domains and induce phase separation. Conversely, lipid phase separation stabilizes protein condensate formation suggesting strong coupling between lipid- and protein-based phase separation. Furthermore, experiments in T-cells show that LAT/Grb2/Sos1 condensates recruit ordered domain lipids and proteins in living cells. We observed that crosslinking of a membrane component that prefers ordered domains (i.e. the endogenous GPI-anchored protein Thy1) stabilizes lipid phase separation and templates condensate formation. Finally, we tested whether condensate-domain coupling is necessary for T-cell activation by decoupling raft domains from condensates through either mutation of the transmembrane domain to modulate its raft affinity or mutation of residues necessary for condensate formation. We found that the coupling of cytoplasmic condensate formation to lipid rafts is essential for T-cell activation. Thus, we conclude that the thermodynamic coupling between LAT/Grb2/Sos1 cytoplasmic condensates and lipid rafts can cooperatively and functionally reorganize the membrane to facilitate T-cell activation.

Hybrid polymer/lipid vesicles: Insights on phase separation and dynamics from time-resolved fluorescence and microscopy.

Recently, hybrid polymer/lipid vesicles were introduced e.g. for drug delivery comprising bimolecular recognition, and the aim is to blend into a single entity the advantages of both different and well established systems, liposomes and polymersomes (vesicles of pure polymer), allowing a fine tuning of stability, bifunctionality and permeability. A comprehensive study of phase separation and domain formation in Giant Hybrid Unilamellar Vesicles (GHUV) was carried out, using several types of polymers and lipids, considering both architecture (grafted, triblock) and molar mass variations. The micro-domains were directly visualized by confocal imaging using suitable labeled polymers and lipids, and FRET-FLIM was used for the detection of nano-domains below microscopy resolution. The sizes, stability and morphology of the observed phase separation are as predictable, dependent on the lipid/molar fraction, but other factors such as the line tension at the domain boundaries, which is fine tuned by the molar mass and polymer architecture, are ruling factors. The lateral diffusion of lipid within polymer chains was determined by FRAP, and it was concluded that no progressive (intermediate) effect is induced by the lipid, the presence of lipid domains playing a clear role.

Polyunsaturated lipids promote membrane phase separation and antimicrobial sensitivity.

Gram-negative bacteria such as Acinetobacter baumannii sequester host lipids from the site of infection for incorporation into lipid synthesis pathways, altering the membrane lipidome. Changes in membrane composition from the incorporation of host-derived polyunsaturated fatty acids (PUFAs) help restore sensitivity to antimicrobials in several species of Gram-negative bacteria. Using coarse-grained simulations based on lipidomic data of A. baumannii inner membrane collected under three different growth conditions, we show PUFA-incorporation alters membrane biophysical properties, increasing the phase separation between ordered and disordered lipid domains resulting in thinner, less ordered membranes. We show that the changes in A. baumannii membrane biophysical properties on the incorporation of PUFA-containing lipids alter the conformational cycling of RND multidrug efflux pumps and restore sensitivity to some antimicrobials. Finally, we examine the interaction of antimicrobial peptides (AMP) with the simulated A. baumannii membranes to identify the effect of lipid saturation and alterations in membrane properties has on AMP-induced membrane disruption.

Phase separation on giant liposomes prepared by gel-assisted swelling.

Giant unilamellar vesicles (GUVs) are often used as models to study lipid membrane structure and function. The most common method for GUV formation is electroformation, though this technique has its own inherent drawbacks such as low yield in ionic solutions or in the presence of charged lipids. In recent years, the method of gel-assisted swelling has been explored as an alternative for electroformation and has been reported to overcome some of the limitations of this technique. This study aims to assess the ability of gel-assisted swelling to form GUVs of ternary lipid compositions that are known to undergo phase separation. To this end, we utilize different ratios of a 3-component mixture of DOPC/DPPC/Cholesterol to form vesicles capable of separating into phases of liquid-ordered (Lo) and liquid-disordered (Ld). This lipid composition was chosen as previous studies have shown that at room temperature, many of its possible compositions exhibit distinct phase separation. We apply confocal fluorescence microscopy to evaluate the resultant GUVs, in terms of yield, size, and phase behavior. We compare the results of this method to that of electroformation with a focus on GUV size and quantity, as well as formation of lipid domains, their number and area fraction on GUVs. Ultimately, the results show that agarose gel-assisted swelling can parallel electroformation in forming phase-separating GUVs over a series of ternary lipid compositions.

Unraveling propylene glycol-induced lipolysis of the biosynthesis pathway in ultra-high temperature milk using high resolution mass spectrometry untargeted lipidomics and proteomics

In July 2022, the food safety accident that excessive propylene glycol was detected in milk processing factory raised widespread concerns about quality and nutrition of milk with illegal additive. To the best of our knowledge, the influences of propylene glycol to lipids in milk had not been systematically explored. Therefore, spatiotemporal distributions of lipids related to propylene glycol reaction and changes of sensory quality were investigated by food exogenous. Briefly, 10 subclasses (Cer, DG, HexCer, LPC, LPE, PC, PE, PI, SPH and TG) included 147 lipids and 38 pivotal enzymes were annotated. Propylene glycol altered lysophospholipidase and phospholipase A2 through altering structural order in lipids domains surrounding proteins to inhibit glycerophospholipid metabolism and initiated obvious changes in PC (10.45–27.91 mg kg−1) and PE (12.92–49.02 mg kg−1). This study offered insights into influences of propylene glycol doses and storage time on milk metabolism at molecular level to assess the quality of milk.

The interplay of membrane fluidity, acyl chain order and area per lipid on the partitioning of two antidepressants paroxetine and sertraline.

Selective serotonin reuptake inhibitors (SSRIs) are among the popular drugs for treating depression and mental disorders. Membrane fluidity has previously been considered as the main factor in modulating the membrane partitioning of SSRIs, while other biophysical properties, such as the acyl chain order and area per lipid, were often neglected. Varying the lipid membrane composition and temperature can significantly modify the physical phase and, in turn, affect its fluidity, acyl chain order and area per lipid. Here, we investigate the role of membrane fluidity, acyl chain order and area per lipid in the partitioning of two SSRIs, paroxetine (PAX) and sertraline (SER). The model membranes were either POPC : SM (1 : 1 mol ratio) or POPC : SM : Chol (1 : 1 : 1 mol ratio) and studied in the temperature range of 25-45 °C. The order parameters and area per lipid in the two lipid mixtures were calculated using molecular dynamics simulations. The membrane partitioning of PAX and SER was determined via second derivative spectrophotometry. In a lower temperature range (25-32 °C), membrane fluidity favors the SSRI partitioning into Lo/Ld POPC:SM:Chol. In a higher temperature range (37-45 °C), the interplay between membrane fluidity, acyl chain order and area per lipid favors drug partitioning into Ld POPC:SM. The findings offer indication for the inconsistent distribution of SSRIs in tissues as well as the possible interaction of SSRIs with lipid domains and membrane-bound proteins.

The Role of Lipid Domains and Physical Properties of Membranes in the Development of Age-Related Neurodegenerative Diseases

The Role of Lipid Domains and Physical Properties of Membranes in the Development of Age-Related Neurodegenerative Diseases