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Emerging Topics in Life Sciences Mar 2023The distinctive feature of Gram-negative bacteria is the presence of an asymmetric outer membrane (OM), which acts as a permeation barrier blocking the diffusion of... (Review)
Review
The distinctive feature of Gram-negative bacteria is the presence of an asymmetric outer membrane (OM), which acts as a permeation barrier blocking the diffusion of noxious components such as antibiotics that could compromise cell survival. The outer membrane has an inner leaflet, mainly formed by phospholipids (PLs), and the outer leaflet, composed of molecules of lipopolysaccharide (LPS). Building this membrane is a very complex process as every OM element needs to be transported from the cytoplasm or the inner membrane and properly placed in the OM. In addition, the asymmetry needs to be maintained to guarantee the barrier function of the membrane. The presence of misplaced PLs in the outer leaflet of the OM causes increased permeability, endangering cell survival. The Mla system (maintenance of OM lipid asymmetry) has been linked to the removal of the misplaced PLs, restoring OM asymmetry. The Mla system has elements in all compartments of the cell envelope: the lipoprotein MlaA in complex with the trimeric porins OmpC/F in the OM, MlaC in the periplasmic space and an ABC transporter in the inner membrane called MlaFEDB. While genetic and structural work suggest that the Mla pathway is retrograde (PL movement from OM to IM), several groups have advocated that transport could happen in an anterograde fashion (from IM to OM). However, recent biochemical studies strongly support retrograde transport. This review provides an overview of the current knowledge of the Mla system from a structural point of view and addresses the latest biochemical findings and their impact in transport directionality.
Topics: Phospholipids; Biological Transport; Membrane Lipids; Cell Membrane; Diffusion
PubMed: 36459067
DOI: 10.1042/ETLS20220087 -
Biochimica Et Biophysica Acta Sep 2015Biological membranes are essential for normal function and regulation of cells, forming a physical barrier between extracellular and intracellular space and cellular... (Review)
Review
Biological membranes are essential for normal function and regulation of cells, forming a physical barrier between extracellular and intracellular space and cellular compartments. These physical barriers are subject to mechanical stresses. As a consequence, nature has developed proteins that are able to transpose mechanical stimuli into meaningful intracellular signals. These proteins, termed Mechanosensitive (MS) proteins provide a variety of roles in response to these stimuli. In prokaryotes these proteins form transmembrane spanning channels that function as osmotically activated nanovalves to prevent cell lysis by hypoosmotic shock. In eukaryotes, the function of MS proteins is more diverse and includes physiological processes such as touch, pain and hearing. The transmembrane portion of these channels is influenced by the physical properties such as charge, shape, thickness and stiffness of the lipid bilayer surrounding it, as well as the bilayer pressure profile. In this review we provide an overview of the progress to date on advances in our understanding of the intimate biophysical and chemical interactions between the lipid bilayer and mechanosensitive membrane channels, focusing on current progress in both eukaryotic and prokaryotic systems. These advances are of importance due to the increasing evidence of the role the MS channels play in disease, such as xerocytosis, muscular dystrophy and cardiac hypertrophy. Moreover, insights gained from lipid-protein interactions of MS channels are likely relevant not only to this class of membrane proteins, but other bilayer embedded proteins as well. This article is part of a Special Issue entitled: Lipid-protein interactions.
Topics: Animals; Cell Membrane; Humans; Lipid Bilayers; Mechanotransduction, Cellular; Membrane Lipids; Membrane Proteins; Models, Molecular; Protein Binding; Protein Structure, Tertiary
PubMed: 25922225
DOI: 10.1016/j.bbamem.2015.04.012 -
Nature Communications Aug 2020Lipid membranes, nucleic acids, proteins, and metabolism are essential for modern cellular life. Synthetic systems emulating the fundamental properties of living cells...
Lipid membranes, nucleic acids, proteins, and metabolism are essential for modern cellular life. Synthetic systems emulating the fundamental properties of living cells must therefore be built upon these functional elements. In this work, phospholipid-producing enzymes encoded in a synthetic minigenome are cell-free expressed within liposome compartments. The de novo synthesized metabolic pathway converts precursors into a variety of lipids, including the constituents of the parental liposome. Balanced production of phosphatidylethanolamine and phosphatidylglycerol is realized, owing to transcriptional regulation of the activity of specific genes combined with a metabolic feedback mechanism. Fluorescence-based methods are developed to image the synthesis and membrane incorporation of phosphatidylserine at the single liposome level. Our results provide experimental evidence for DNA-programmed membrane synthesis in a minimal cell model. Strategies are discussed to alleviate current limitations toward effective liposome growth and self-reproduction.
Topics: Escherichia coli; Gene Expression; Liposomes; Membrane Lipids; Phosphatidylethanolamines; Phosphatidylglycerols; Phospholipids; Proteomics
PubMed: 32859896
DOI: 10.1038/s41467-020-17863-5 -
Biochemical Society Transactions Feb 2017The application of membrane proteins in biotechnology requires robust, durable reconstitution systems that enhance their stability and support their functionality in a... (Review)
Review
The application of membrane proteins in biotechnology requires robust, durable reconstitution systems that enhance their stability and support their functionality in a range of working environments. Vesicular architectures are highly desirable to provide the compartmentalisation to utilise the functional transmembrane transport and signalling properties of membrane proteins. Proteoliposomes provide a native-like membrane environment to support membrane protein function, but can lack the required chemical and physical stability. Amphiphilic block copolymers can also self-assemble into polymersomes: tough vesicles with improved stability compared with liposomes. This review discusses the reconstitution of membrane proteins into polymersomes and the more recent development of hybrid vesicles, which blend the robust nature of block copolymers with the biofunctionality of lipids. These novel synthetic vesicles hold great promise for enabling membrane proteins within biotechnologies by supporting their enhanced performance and could also contribute to fundamental biochemical and biophysical research by improving the stability of membrane proteins that are challenging to work with.
Topics: Biological Transport; Biotechnology; Lipid Bilayers; Membrane Lipids; Membrane Proteins; Models, Chemical; Models, Molecular; Polymers; Proteolipids; Unilamellar Liposomes
PubMed: 28202656
DOI: 10.1042/BST20160019 -
International Journal of Molecular... Oct 2023Biological membranes, primarily composed of lipids, envelop each living cell. The intricate composition and organization of membrane lipids, including the variety of... (Review)
Review
Biological membranes, primarily composed of lipids, envelop each living cell. The intricate composition and organization of membrane lipids, including the variety of fatty acids they encompass, serve a dynamic role in sustaining cellular structural integrity and functionality. Typically, modifications in lipid composition coincide with consequential alterations in universally significant signaling pathways. Exploring the various fatty acids, which serve as the foundational building blocks of membrane lipids, provides crucial insights into the underlying mechanisms governing a myriad of cellular processes, such as membrane fluidity, protein trafficking, signal transduction, intercellular communication, and the etiology of certain metabolic disorders. Furthermore, comprehending how alterations in the lipid composition, especially concerning the fatty acid profile, either contribute to or prevent the onset of pathological conditions stands as a compelling area of research. Hence, this review aims to meticulously introduce the intricacies of membrane lipids and their constituent fatty acids in a healthy organism, thereby illuminating their remarkable diversity and profound influence on cellular function. Furthermore, this review aspires to highlight some potential therapeutic targets for various pathological conditions that may be ameliorated through dietary fatty acid supplements. The initial section of this review expounds on the eukaryotic biomembranes and their complex lipids. Subsequent sections provide insights into the synthesis, membrane incorporation, and distribution of fatty acids across various fractions of membrane lipids. The last section highlights the functional significance of membrane-associated fatty acids and their innate capacity to shape the various cellular physiological responses.
Topics: Fatty Acids; Membrane Lipids; Cell Membrane; Membrane Fluidity; Eukaryota; Phospholipids
PubMed: 37958678
DOI: 10.3390/ijms242115693 -
Biochimica Et Biophysica Acta.... Feb 2022Methods for efficient cyclodextrin-induced lipid exchange have been developed in our lab. These make it possible to almost completely replace the lipids in the outer... (Review)
Review
Methods for efficient cyclodextrin-induced lipid exchange have been developed in our lab. These make it possible to almost completely replace the lipids in the outer leaflet of artificial membranes or the plasma membranes of living cells with exogenous lipids. Lipid replacement/substitution allows detailed studies of how lipid composition and asymmetry influence the structure and function of membrane domains and membrane proteins. In this review, we both summarize progress on cyclodextrin exchange in cells, mainly by the use of methyl-alpha cyclodextrin to exchange phospholipids and sphingolipids, and discuss the issues to consider when carrying out lipid exchange experiments upon cells. Issues that impact interpretation of lipid exchange are also discussed. This includes how overly naïve interpretation of how lipid exchange-induced changes in domain formation can impact protein function.
Topics: Lipid Metabolism; Membrane Lipids; Membrane Microdomains; Membrane Proteins; Mutation, Missense; Phospholipids; alpha-Cyclodextrins
PubMed: 34534531
DOI: 10.1016/j.bbamem.2021.183774 -
Biochimica Et Biophysica Acta Jan 2009The pulsed field gradient (pfg)-NMR method for measurements of translational diffusion of molecules in macroscopically aligned lipid bilayers is described. This... (Review)
Review
The pulsed field gradient (pfg)-NMR method for measurements of translational diffusion of molecules in macroscopically aligned lipid bilayers is described. This technique is proposed to have an appreciable potential for investigations in the field of lipid and membrane biology. Transport of molecules in the plane of the bilayer can be successfully studied, as well as lateral phase separation of lipids and their dynamics within the bilayer organizations. Lateral diffusion coefficients depend on lipid packing and acyl chain ordering and investigations of order parameters of perdeuterated acyl chains, using (2)H NMR quadrupole splittings, are useful complements. In this review we summarize some of our recent achievements obtained on lipid membranes. In particular, bilayers exhibiting two-phase coexistence of liquid disordered (l(d)) and liquid ordered (l(o)) phases are considered in detail. Methods for obtaining good oriented lipid bilayers, necessary for the pfg-NMR method to be efficiently used, are also briefly described. Among our major results, besides determinations of l(d) and l(o) phases, belongs the finding that the lateral diffusion is the same for all components, independent of the molecular structure (including cholesterol (CHOL)), if they reside in the same domain or phase in the membrane. Furthermore, quite unexpectedly CHOL seems to partition into the l(d)and l(o) phases to roughly the same extent, indicating that CHOL has no strong preference for any of these phases, i.e. CHOL seems to have similar interactions with all of the lipids. We propose that the lateral phase separation in bilayers containing one high-T(m) and one low-T(m) lipid together with CHOL is driven by the increasing difficulty of incorporating an unsaturated or prenyl lipid into the highly ordered bilayer formed by a saturated lipid and CHOL, i.e. the phase transition is entropy driven to keep the disorder of the hydrocarbon chains of the unsaturated lipid.
Topics: Diffusion; Hydrophobic and Hydrophilic Interactions; Lipid Bilayers; Magnetic Resonance Spectroscopy; Membrane Fluidity; Membrane Lipids; Membranes; Models, Biological; Models, Chemical; Molecular Structure
PubMed: 18805393
DOI: 10.1016/j.bbamem.2008.08.016 -
The FEBS Journal Dec 2020Proteins are essential and abundant components of cellular membranes. Being densely packed within the limited surface area, proteins fulfil essential tasks for life,... (Review)
Review
Proteins are essential and abundant components of cellular membranes. Being densely packed within the limited surface area, proteins fulfil essential tasks for life, which include transport, signalling and maintenance of cellular homeostasis. The high protein density promotes nonspecific interactions, which affect the dynamics of the membrane-associated processes, but also contribute to higher levels of membrane organization. Here, we provide a comprehensive summary of the most recent findings of diverse effects resulting from high protein densities in both living membranes and reconstituted systems and display why the crowding phenomenon should be considered and assessed when studying cellular pathways. Biochemical, biophysical and computational studies reveal effects of crowding on the translational mobility of proteins and lipids, oligomerization and clustering of integral membrane proteins, and also folding and aggregation of proteins at the lipid membrane interface. The effects of crowding pervade to larger length scales, where interfacial and transmembrane crowding shapes the lipid membrane. Finally, we discuss the design and development of fluorescence-based sensors for macromolecular crowding and the perspectives to use those in application to cellular membranes and suggest some emerging topics in studying crowding at biological interfaces.
Topics: Animals; Cell Membrane; Humans; Macromolecular Substances; Membrane Lipids; Membrane Proteins; Molecular Conformation
PubMed: 32463979
DOI: 10.1111/febs.15429 -
Biochimica Et Biophysica Acta.... Nov 2021Sphingolipids can be differentiated from other membrane lipids by the distinctive chemistry of the sphingoid long chain base (LCB), which is generated by the... (Review)
Review
Sphingolipids can be differentiated from other membrane lipids by the distinctive chemistry of the sphingoid long chain base (LCB), which is generated by the condensation of an amino acid (normally but not always serine) and a fatty acyl CoA (normally palmitoyl CoA) by the pyridoxal phosphate-dependent enzyme, serine palmitoyl transferase (SPT). The first five carbon atoms of the sphingoid LCB, herein defined as the 'sphingoid motif', are largely responsible for the unique chemical and biophysical properties of sphingolipids since they can undergo a relatively large number (compared to other lipid species) of molecular interactions with other membrane lipids, via hydrogen-bonding, charge-pairing, hydrophobic and van der Waals interactions. These interactions are responsible, for instance, for the association of sphingolipids with cholesterol in the membrane lipid bilayer. Here, we discuss some of the unique properties of this sphingoid motif, and in addition to outlining how this structural motif drives intra-bilayer interactions, discuss the atomic details of the interactions with two critical players in the biosynthetic pathway, namely SPT, and the ceramide transport protein, CERT. In the former, the selectivity of sphingolipid synthesis relies on a hydrogen bond interaction between Lys379 of SPTLC2 and the l-serine sidechain hydroxyl moiety. In the latter, the entire sphingoid motif is stereoselectively recognized by a hydrogen-bonding network involving all three sphingoid motif heteroatoms. The remarkable selectivity of these interactions, and the subtle means by which these interactions are modified and regulated in eukaryotic cells raises a number of challenging questions about the generation of these proteins, and of their interactions with the sphingoid motif in evolutionary history.
Topics: Cell Membrane; Hydrogen Bonding; Membrane Lipids; Molecular Structure; Sphingolipids
PubMed: 34302797
DOI: 10.1016/j.bbamem.2021.183701 -
Nutrients May 2023Alterations in membrane lipids are reported in schizophrenia. However, no conclusion can be drawn regarding the extended and predictive value of these alterations in...
Alterations in membrane lipids are reported in schizophrenia. However, no conclusion can be drawn regarding the extended and predictive value of these alterations in persons at ultra-high risk of psychosis (UHR). Recent studies suggested that sterols' impact on psychiatric disorders was underestimated. Here, we simultaneously explored sterols, fatty acids (FA), and phospholipids (PL) in UHR persons for the first time. We analysed erythrocyte membrane lipids in 61 UHR persons, including 29 who later converted to psychosis (UHR-C) and 32 who did not (UHC-NC). We used gas chromatography for and liquid chromatography tandem with mass spectrometry for sterols and phospholipids. Among UHR individuals, elevated baseline membrane linoleic acid level was associated with conversion to psychosis (26.1% vs. 60.5%, = 0.02). Combining sterols, FA, and PL membrane composition improved the prediction of psychosis onset (AUC = 0.73). This is the first report showing that membrane sterol participates, with other membrane lipids, in modulating the risk of psychosis. It suggests that membrane lipids could be used as biomarkers for personalised medicine in UHR patients.
Topics: Humans; Membrane Lipids; Gas Chromatography-Mass Spectrometry; Psychotic Disorders; Sterols; Phospholipids; Phytosterols; Fatty Acids; Biomarkers
PubMed: 37432345
DOI: 10.3390/nu15092215