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Cold Spring Harbor Perspectives in... May 2011Cells have thousands of different lipids. In the plasma membrane, and in membranes of the late secretory and endocytotic pathways, these lipids are not evenly... (Review)
Review
Cells have thousands of different lipids. In the plasma membrane, and in membranes of the late secretory and endocytotic pathways, these lipids are not evenly distributed over the two leaflets of the lipid bilayer. The basis for this transmembrane lipid asymmetry lies in the fact that glycerolipids are primarily synthesized on the cytosolic and sphingolipids on the noncytosolic surface of cellular membranes, that cholesterol has a higher affinity for sphingolipids than for glycerolipids. In addition, P4-ATPases, "flippases," actively translocate the aminophospholipids phosphatidylserine and phosphatidylethanolamine to the cytosolic surface. ABC transporters translocate lipids in the opposite direction but they generally act as exporters rather than "floppases." The steady state asymmetry of the lipids can be disrupted within seconds by the activation of phospholipases and scramblases. The asymmetric lipid distribution has multiple implications for physiological events at the membrane surface. Moreover, the active translocation also contributes to the generation of curvature in the budding of transport vesicles.
Topics: Bacteria; Biological Transport; Cell Membrane; Lipid Bilayers; Lipid Metabolism; Membrane Lipids; Mitochondrial Membranes; Models, Biological; Models, Molecular; Transport Vesicles; Viruses
PubMed: 21436058
DOI: 10.1101/cshperspect.a004671 -
Chemical Reviews Mar 2024It is well-known that aqueous dispersions of phospholipids spontaneously assemble into bilayer structures. These structures have numerous applications across chemistry... (Review)
Review
It is well-known that aqueous dispersions of phospholipids spontaneously assemble into bilayer structures. These structures have numerous applications across chemistry and materials science and form the fundamental structural unit of the biological membrane. The particular environment of the lipid bilayer, with a water-poor low dielectric core surrounded by a more polar and better hydrated interfacial region, gives the membrane particular biophysical and physicochemical properties and presents a unique environment for chemical reactions to occur. Many different types of molecule spanning a range of sizes, from dissolved gases through small organics to proteins, are able to interact with membranes and promote chemical changes to lipids that subsequently affect the physicochemical properties of the bilayer. This Review describes the chemical reactivity exhibited by lipids in their membrane form, with an emphasis on conditions where the lipids are well hydrated in the form of bilayers. Key topics include the following: lytic reactions of glyceryl esters, including hydrolysis, aminolysis, and transesterification; oxidation reactions of alkenes in unsaturated fatty acids and sterols, including autoxidation and oxidation by singlet oxygen; reactivity of headgroups, particularly with reactive carbonyl species; and / isomerization of alkenes. The consequences of reactivity for biological activity and biophysical properties are also discussed.
Topics: Membrane Lipids; Lipid Bilayers; Cell Membrane; Membranes; Phospholipids; Alkenes
PubMed: 38498932
DOI: 10.1021/acs.chemrev.3c00608 -
Biochimica Et Biophysica Acta Sep 2015Cell membranes are composed of a lipid bilayer containing proteins that cross and/or interact with lipids on either side of the two leaflets. The basic structure of cell... (Review)
Review
Cell membranes are composed of a lipid bilayer containing proteins that cross and/or interact with lipids on either side of the two leaflets. The basic structure of cell membranes is this bilayer, composed of two opposing lipid monolayers with fascinating properties designed to perform all the functions the cell requires. To coordinate these functions, lipid composition of cellular membranes is tailored to suit their specialized tasks. In this review, we describe the general mechanisms of membrane-protein interactions and relate them to some of the molecular strategies organisms use to adjust the membrane lipid composition in response to a decrease in environmental temperature. While the activities of all biomolecules are altered as a function of temperature, the thermosensors we focus on here are molecules whose temperature sensitivity appears to be linked to changes in the biophysical properties of membrane lipids. This article is part of a Special Issue entitled: Lipid-protein interactions.
Topics: Animals; Humans; Lipid Bilayers; Membrane Lipids; Membrane Proteins; Models, Molecular; Protein Binding; Protein Structure, Tertiary; Temperature; Thermosensing
PubMed: 25906947
DOI: 10.1016/j.bbamem.2015.04.005 -
Cold Spring Harbor Perspectives in... Oct 2011Cell membranes are composed of a lipid bilayer, containing proteins that span the bilayer and/or interact with the lipids on either side of the two leaflets. Although... (Review)
Review
Cell membranes are composed of a lipid bilayer, containing proteins that span the bilayer and/or interact with the lipids on either side of the two leaflets. Although recent advances in lipid analytics show that membranes in eukaryotic cells contain hundreds of different lipid species, the function of this lipid diversity remains enigmatic. The basic structure of cell membranes is the lipid bilayer, composed of two apposing leaflets, forming a two-dimensional liquid with fascinating properties designed to perform the functions cells require. To coordinate these functions, the bilayer has evolved the propensity to segregate its constituents laterally. This capability is based on dynamic liquid-liquid immiscibility and underlies the raft concept of membrane subcompartmentalization. This principle combines the potential for sphingolipid-cholesterol self-assembly with protein specificity to focus and regulate membrane bioactivity. Here we will review the emerging principles of membrane architecture with special emphasis on lipid organization and domain formation.
Topics: Animals; Biological Transport; Cell Line; Dogs; Endoplasmic Reticulum; Golgi Apparatus; Lipid Bilayers; Membrane Lipids; Membrane Microdomains; Membrane Proteins; Models, Biological; Sphingolipids; Sterols; Yeasts
PubMed: 21628426
DOI: 10.1101/cshperspect.a004697 -
Cold Spring Harbor Perspectives in... Nov 2011Morphological plasticity of biological membrane is critical for cellular life, as cells need to quickly rearrange their membranes. Yet, these rearrangements are... (Review)
Review
Morphological plasticity of biological membrane is critical for cellular life, as cells need to quickly rearrange their membranes. Yet, these rearrangements are constrained in two ways. First, membrane transformations may not lead to undesirable mixing of, or leakage from, the participating cellular compartments. Second, membrane systems should be metastable at large length scales, ensuring the correct function of the particular organelle and its turnover during cellular division. Lipids, through their ability to exist with many shapes (polymorphism), provide an adequate construction material for cellular membranes. They can self-assemble into shells that are very flexible, albeit hardly stretchable, which allows for their far-reaching morphological and topological behaviors. In this article, we will discuss the importance of lipid polymorphisms in the shaping of membranes and its role in controlling cellular membrane morphology.
Topics: Cell Membrane; Cell Shape; Lipid Bilayers; Membrane Lipids; Membrane Proteins
PubMed: 21646378
DOI: 10.1101/cshperspect.a004747 -
Protein Science : a Publication of the... Jun 2020Our understanding of the plasma membrane structure has undergone a major change since the proposal of the fluid mosaic model of Singer and Nicholson in the 1970s. In... (Review)
Review
Our understanding of the plasma membrane structure has undergone a major change since the proposal of the fluid mosaic model of Singer and Nicholson in the 1970s. In this model, the membrane, composed of over thousand lipid and protein species, is organized as a well-equilibrated two-dimensional fluid. Here, the distribution of lipids is largely expected to reflect a multicomponent system, and proteins are expected to be surrounded by an annulus of specialized lipid species. With the recognition that a multicomponent lipid membrane is capable of phase segregation, the membrane is expected to appear as patchwork quilt pattern of membrane domains. However, the constituents of a living membrane are far from being well equilibrated. The living cell membrane actively maintains a trans-bilayer asymmetry of composition, and its constituents are subject to a number of dynamic processes due to synthesis, lipid transfer as well as membrane traffic and turnover. Moreover, membrane constituents engage with the dynamic cytoskeleton of a living cell, and are both passively as well as actively manipulated by this engagement. The extracellular matrix and associated elements also interact with membrane proteins contributing to another layer of interaction. At the nano- and mesoscale, the organization of lipids and proteins emerge from these encounters, as well as from protein-protein, protein-lipid, and lipid-lipid interactions in the membrane. New methods to study the organization of membrane components at these scales have also been developed, and provide an opportunity to synthesize a new picture of the living cell surface as an active membrane composite.
Topics: Animals; Cell Membrane; Humans; Lipids; Membrane Lipids
PubMed: 32297381
DOI: 10.1002/pro.3874 -
Chemistry and Physics of Lipids Jul 2023Labyrinthopeptins constitute a class of ribosomal synthesized peptides belonging to the type III family of lantibiotics. They exist in different variants and display...
Labyrinthopeptins constitute a class of ribosomal synthesized peptides belonging to the type III family of lantibiotics. They exist in different variants and display broad antiviral activities as well as show antiallodynic activity. Although their mechanism of action is not understood, it has been described that Labyrinthopeptins interact with membrane phospholipids modulating its biophysical properties and point out to membrane destabilization as its main point of action. We have used all-atom molecular dynamics to study the location of labyrinthopeptin A2 in a complex membrane as well as the existence of specific interactions with membrane lipids. Our results indicate that labyrinthopeptin A2, maintaining its globular structure, tends to be placed at the membrane interface, mainly between the phosphate atoms of the phospholipids and the oxygen atom of cholesterol modulating the biophysical properties of the membrane lipids. Outstandingly, we have found that labyrinthopeptin A2 tends to be preferentially surrounded by sphingomyelin while excluding cholesterol. The bioactive properties of labyrinthopeptin A2 could be attributed to the specific disorganization of raft domains in the membrane and the concomitant disruption of the overall membrane organization. These results support the improvement of Labyrinthopeptins as therapeutic molecules, opening up new opportunities for future medical advances.
Topics: Membrane Lipids; Phospholipids; Bacteriocins; Cholesterol; Membrane Microdomains
PubMed: 37061155
DOI: 10.1016/j.chemphyslip.2023.105303 -
Cold Spring Harbor Perspectives in... Aug 2014Mycobacterium tuberculosis (Mtb) lipids are indelibly imprinted in just about every key aspect of tuberculosis (TB) basic and translational research. Although the... (Review)
Review
Mycobacterium tuberculosis (Mtb) lipids are indelibly imprinted in just about every key aspect of tuberculosis (TB) basic and translational research. Although the interest in these compounds originally stemmed from their abundance, structural diversity, and antigenicity, continued research in this field has been driven by their important contribution to TB pathogenesis and their interest from the perspective of drug, vaccine, diagnostic, and biomarker development. This article summarizes what is known of the roles of lipids in the physiology and pathogenicity of Mtb and the exciting developments that have occurred in recent years in identifying new lead compounds targeting their biogenesis.
Topics: Cell Membrane; Drug Design; Lipopolysaccharides; Membrane Lipids; Molecular Structure; Mycobacterium tuberculosis; Mycolic Acids; Signal Transduction; Terpenes
PubMed: 25104772
DOI: 10.1101/cshperspect.a021105 -
Virulence Dec 2021Lipids are complex organic compounds made up of carbon, oxygen, and hydrogen. These play a diverse and intricate role in cellular processes like membrane trafficking,... (Review)
Review
Lipids are complex organic compounds made up of carbon, oxygen, and hydrogen. These play a diverse and intricate role in cellular processes like membrane trafficking, protein sorting, signal transduction, and bacterial infections. Both Gram-positive bacteria (.) and Gram-negative bacteria (, etc.) can hijack the various host-lipids and utilize them structurally as well as functionally to mount a successful infection. The pathogens can deploy with various arsenals to exploit host membrane lipids and lipid-associated receptors as an attachment for toxins' landing or facilitate their entry into the host cellular niche. Bacterial species like sp. can also modulate the host lipid metabolism to fetch its carbon source from the host. The sequential conversion of host membrane lipids into arachidonic acid and prostaglandin E2 due to increased activity of cPLA-2 and COX-2 upon bacterial infection creates immunosuppressive conditions and facilitates the intracellular growth and proliferation of bacteria. However, lipids' more debatable role is that they can also be a blessing in disguise. Certain host-lipids, especially sphingolipids, have been shown to play a crucial antibacterial role and help the host in combating the infections. This review shed light on the detailed role of host lipids in bacterial infections and the current understanding of the lipid in therapeutics. We have also discussed potential prospects and the need of the hour to help us cope in this race against deadly pathogens and their rapidly evolving stealthy virulence strategies.
Topics: Animals; Bacteria; Bacterial Infections; Gram-Negative Bacteria; Gram-Positive Bacteria; Host-Pathogen Interactions; Humans; Lipid Metabolism; Membrane Lipids; Mice; Signal Transduction; Virulence
PubMed: 33356849
DOI: 10.1080/21505594.2020.1869441 -
Annual Review of Physical Chemistry Apr 2021Lateral organization in the plane of the plasma membrane is an important driver of biological processes. The past dozen years have seen increasing experimental support... (Review)
Review
Lateral organization in the plane of the plasma membrane is an important driver of biological processes. The past dozen years have seen increasing experimental support for the notion that lipid organization plays an important role in modulating this heterogeneity. Various biophysical mechanisms rooted in the concept of liquid-liquid phase separation have been proposed to explain diverse experimental observations of heterogeneity in model and cell membranes with distinct but overlapping applicability. In this review, we focus on the evidence for and the consequences of the hypothesis that the plasma membrane is poised near an equilibrium miscibility critical point. Critical phenomena explain certain features of the heterogeneity observed in cells and model systems but also go beyond heterogeneity to predict other interesting phenomena, including responses to perturbations in membrane composition.
Topics: Cell Membrane; Eukaryotic Cells; Membrane Lipids; Membrane Microdomains; Membrane Proteins
PubMed: 33710910
DOI: 10.1146/annurev-physchem-090419-115951