Inflammatory caspases (caspases 1, 4, 5 and 11) are activated in response to microbial infection and danger signals. When activated, they cleave mouse and human gasdermin D (GSDMD) after Asp276 and ...Asp275, respectively, to generate an N-terminal cleavage product (GSDMD-NT) that triggers inflammatory death (pyroptosis) and release of inflammatory cytokines such as interleukin-1β. Cleavage removes the C-terminal fragment (GSDMD-CT), which is thought to fold back on GSDMD-NT to inhibit its activation. However, how GSDMD-NT causes cell death is unknown. Here we show that GSDMD-NT oligomerizes in membranes to form pores that are visible by electron microscopy. GSDMD-NT binds to phosphatidylinositol phosphates and phosphatidylserine (restricted to the cell membrane inner leaflet) and cardiolipin (present in the inner and outer leaflets of bacterial membranes). Mutation of four evolutionarily conserved basic residues blocks GSDMD-NT oligomerization, membrane binding, pore formation and pyroptosis. Because of its lipid-binding preferences, GSDMD-NT kills from within the cell, but does not harm neighbouring mammalian cells when it is released during pyroptosis. GSDMD-NT also kills cell-free bacteria in vitro and may have a direct bactericidal effect within the cytosol of host cells, but the importance of direct bacterial killing in controlling in vivo infection remains to be determined.
Membranes play an enormous role in our life. Biological cell membranes control the fluxes of substances in and out of cells. Artificial membranes are widely used in numerous applications including ...“green” separation processes in chemistry, agroindustry, biology, medicine; they are used as well in energy generation from renewable sources. They largely mimic the structure and functions of biological membranes. The similarity in the structure leads to the similarity in the properties and the approaches to study the laws governing the behavior of both biological and artificial membranes. In this book, some physico-chemical and chemico-physical aspects of the structure and behavior of biological and artificial membranes are investigated.
Nowadays we understand cell membranes not as a simple double lipid layer but as a collection of complex and dynamic protein–lipid structures and microdomains that serve as functional platforms for ...interacting signaling lipids and proteins. Membrane lipids and lipid structures participate directly as messengers or regulators of signal transduction. In addition, protein–lipid interactions participate in the localization of signaling protein partners to specific membrane microdomains. Thus, lipid alterations change cell signaling that are associated with a variety of diseases including cancer, obesity, neurodegenerative disorders, cardiovascular pathologies, etc. This article reviews the newly emerging field of membrane lipid therapy which involves the pharmacological regulation of membrane lipid composition and structure for the treatment of diseases. Membrane lipid therapy proposes the use of new molecules specifically designed to modify membrane lipid structures and microdomains as pharmaceutical disease-modifying agents by reversing the malfunction or altering the expression of disease-specific protein or lipid signal cascades. Here, we provide an in-depth analysis of this emerging field, especially its molecular bases and its relevance to the development of innovative therapeutic approaches.
Dopamine: Just the Right Medicine for Membranes Yang, Hao‐Cheng; Waldman, Ruben Z.; Wu, Ming‐Bang ...
Advanced functional materials,
February 21, 2018, Letnik:
28, Številka:
8
Journal Article
Recenzirano
Odprti dostop
Mussel‐inspired chemistry has attracted widespread interest in membrane science and technology. Demonstrating the rapid growth of this field over the past several years, substantial progress has been ...achieved in both mussel‐inspired chemistry and membrane surface engineering based on mussel‐inspired coatings. At this stage, it is valuable to summarize the most recent and distinctive developments, as well as to frame the challenges and opportunities remaining in this field. In this review, recent advances in rapid and controllable deposition of mussel‐inspired coatings, dopamine‐assisted codeposition technology, and photoinitiated grafting directly on mussel‐inspired coatings are presented. Some of these technologies have not yet been employed directly in membrane science. Beyond discussing advances in conventional membrane processes, emerging applications of mussel‐inspired coatings in membranes are discussed, including as a skin layer in nanofiltration, interlayer in metal‐organic framework based membranes, hydrophilic layer in Janus membranes, and protective layer in catalytic membranes. Finally, some critical unsolved challenges are raised in this field and some potential pathways are proposed to address them.
Mussel‐inspired polydopamine is a rising star in membrane science and technology. The most recent advances in polydopamine deposition are highlighted and summarized, as well as its emerging applications in nanofiltration, metal‐organic framework composite membranes, Janus membranes, and photocatalytic membranes.
Water is a vital element for life and the environment. Water pollution has been documented as a contributor to a wide range of health problems. In recent years, the water quality levels have suffered ...great deterioration because of rapid social and economic development and because it is used to “dump” a wide range of pollutants.This book entitled “Membranes for Water and Wastewater Treatment” contains featured research papers dealing with recent developments and advances in all aspects related to membranes for water and wastewater treatment: membrane processes, combined processes (including one membrane step), modified membranes, new materials, and the possibility to reduce fouling and to improve the efficiency of enhanced processes. The papers compiled in this Special Issue can be read as a response to the current needs and challenges in membrane development for water and wastewater treatment.Half of the research articles correspond to concrete and practical applications of the use of membrane processes in different fields of the industry, with the aim of treating and conditioning water and wastewater. The studies reveal the treatment of industrial streams, mining, recycled paper industry, olive mill, urban wastewater, etc. Another important percentage of studies are related to membrane modification processes, with the aim of obtaining new materials with better performance in the separation processes, thus describing the use of membranes modified with chitosan, nanoparticles, and other organic compounds. This field also includes studies related to fouling and its modeling.
Electroporation or electropermeabilization is a technique that enables transient increase in the cell membrane permeability by exposing cells to pulsed electric field. However, the molecular ...mechanisms of the long-lived cell membrane permeability, which persists on the minutes time scale after the pulse treatment, remain elusive. Experimental studies have suggested that lipid peroxidation could present a mechanism of this prolonged membrane permeabilization. In this study we make the first important step in quantifying the possible contribution of lipid peroxidation to electropermeabilization. We use free energy calculations to quantify the permeability and conductance of bilayers, containing an increasing percentage of hydroperoxide lipid derivatives, to sodium and chloride ions. We then compare our calculations to experimental measurements on electropermeabilized cells. Our results show that the permeability and conductance increase dramatically by several orders of magnitude in peroxidized bilayers. Yet this increase is not sufficient to reasonably account for the entire range of experimental measurements. Nevertheless, lipid peroxidation might be considered an important mechanism of prolonged membrane permeabilization, if exposure of cells to high voltage electric pulses leads to secondary lipid peroxidation products. Our analysis calls for experimental studies, which will determine the type and amount of lipid peroxidation products in electropermeabilized cell membranes.
•Na and Cl ions permeability of peroxidized lipid bilayers is investigated using Unified Free Energy Dynamics simulations.•The contribution of lipid peroxidation to electropermeabilization is quantitatively assessed.•High amounts of peroxidized lipids increase the bilayers permeability and conductance by several orders of magnitude.•Hydroperoxide lipid derivatives are not permeable enough to account for the measured electropermeabilization of cells.
The opening of a nonspecific channel, known as the permeability transition pore (PTP), in the inner membranes of mitochondria can be triggered by calcium ions, leading to swelling of the organelle, ...disruption of the inner membrane and ATP synthesis, and cell death. Pore opening can be inhibited by cyclosporin A mediated via cyclophilin D. It has been proposed that the pore is associated with the dimeric ATP synthase and the oligomycin sensitivity conferral protein (OSCP), a component of the enzyme’s peripheral stalk, provides the site at which cyclophilin D interacts. Subunit b contributes a central α-helical structure to the peripheral stalk, extending from near the top of the enzyme’s catalytic domain and crossing the membrane domain of the enzyme via two α-helices. We investigated the possible involvement of the subunit b and the OSCP in the PTP by generating clonal cells, HAP1-Δb and HAP1-ΔOSCP, lacking the membrane domain of subunit b or the OSCP, respectively, in which the corresponding genes, ATP5F1 and ATP5O, had been disrupted. Both cell lines preserve the characteristic properties of the PTP; therefore, the membrane domain of subunit b does not contribute to the PTP, and the OSCP does not provide the site of interaction with cyclophilin D. The membrane subunits ATP6, ATP8, and subunit c have been eliminated previously from possible participation in the PTP; thus, the only subunits of ATP synthase that could participate in pore formation are e, f, g, diabetes-associated protein in insulin-sensitive tissues (DAPIT), and the 6.8-kDa proteolipid.
This Special Issue is aimed at highlighting the potentialities of membrane and membrane reactor operations in various sectors of chemical engineering, based on application of the process ...intensification strategy. In all of the contributions, the principles of process intensification were pursued during the adoption of membrane technology, demonstrating how it may lead to the development of redesigned processes that are more compact and efficient while also being more environmental friendly, energy saving, and amenable to integration with other green processes.
This Special Issue comprises a number of experimental and theoretical studies dealing with the application of membrane and membrane reactor technology in various scientific fields of chemical engineering, such as membrane distillation for wastewater treatment, hydrogen production from reforming reactions via inorganic membrane and membrane photoassisted reactors, membrane desalination, gas/liquid phase membrane separation of CO2, and membrane filtration for the recovery of antioxidants from agricultural byproducts, contributing to valorization of the potentialities of membrane operations.
Examining the fundamental structure and processes of living cells at the nanoscale poses a unique analytical challenge, as cells are dynamic, chemically diverse, and fragile. A case in point is the ...cell membrane, which is too small to be seen directly with optical microscopy and provides little observational contrast for other methods. As a consequence, nanoscale characterization of the membrane has been performed ex vivo or in the presence of exogenous labels used to enhance contrast and impart specificity. Here, we introduce an isotopic labeling strategy in the gram-positive bacterium Bacillus subtilis to investigate the nanoscale structure and organization of its plasma membrane in vivo. Through genetic and chemical manipulation of the organism, we labeled the cell and its membrane independently with specific amounts of hydrogen (H) and deuterium (D). These isotopes have different neutron scattering properties without altering the chemical composition of the cells. From neutron scattering spectra, we confirmed that the B. subtilis cell membrane is lamellar and determined that its average hydrophobic thickness is 24.3 ± 0.9 Ångstroms (Å). Furthermore, by creating neutron contrast within the plane of the membrane using a mixture of H- and D-fatty acids, we detected lateral features smaller than 40 nm that are consistent with the notion of lipid rafts. These experiments-performed under biologically relevant conditions-answer long-standing questions in membrane biology and illustrate a fundamentally new approach for systematic in vivo investigations of cell membrane structure.
The activities of integral membrane proteins are often affected by the structures of the lipid molecules that surround them in the membrane. One important parameter is the hydrophobic thickness of ...the lipid bilayer, defined by the lengths of the lipid fatty acyl chains. Membrane proteins are not rigid entities, and deform to ensure good hydrophobic matching to the surrounding lipid bilayer. The structure of the lipid headgroup region is likely to be important in defining the structures of those parts of a membrane protein that are located in the lipid headgroup region. A number of examples are given where the conformation of the headgroup-embedded region of a membrane protein changes during the reaction cycle of the protein; activities of such proteins might be expected to be particularly sensitive to lipid headgroup structure. Differences in hydrogen bonding potential and hydration between the headgroups of phosphatidycholines and phosphatidylethanolamines could be important factors in determining the effects of these lipids on protein activities, as well as any effects related to the tendency of the phosphatidylethanolamines to form a curved, hexagonal H
II phase. Effects of lipid structure on protein aggregation and helix–helix interactions are also discussed, as well as the effects of charged lipids on ion concentrations close to the surface of the bilayer. Interpretations of lipid effects in terms of changes in protein volume, lipid free volume, and curvature frustration are also described. Finally, the role of non-annular, or ‘co-factor’ lipids, tightly bound to membrane proteins, is described.
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