DOCSLIB.ORG

The Role of Lipid Domains and Sterol Chemistry in Nanoparticle-Cell Membrane

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
The Role of Lipid Domains and Sterol Chemistry in Nanoparticle-Cell Membrane The Role of Lipid Domains and Sterol Chemistry in Nanoparticle-Cell Membrane Interactions A thesis presented to the faculty of the Russ College of Engineering and Technology of Ohio University In partial fulfillment of the requirements for the degree Master of Science Andrew B. Fuhrer August 2020 © 2020 Andrew B. Fuhrer. All Rights Reserved. 2 This thesis titled The Role of Lipid Domains and Sterol Chemistry in Nanoparticle-Cell Membrane Interactions by ANDREW B. FUHRER has been approved for the Department of Chemical and Biomolecular Engineering and the Russ College of Engineering and Technology by Amir M. Farnoud Assistant Professor of Chemical and Biomolecular Engineering Mei Wei Dean, Russ College of Engineering and Technology 3 Abstract FUHRER, ANDREW B., M.S., August 2020, Biomedical Engineering The Role of Lipid Domains and Sterol Chemistry in Nanoparticle-Cell Membrane Interactions Director of Thesis: Amir M. Farnoud There is a growing interest in the scientific research community to develop nanoparticles for use in novel commercial and biomedical applications, fueled by recent advances in nanotechnology and nanoparticle synthesis. Potential applications for nanoparticles include use as catalysts during chemical manufacturing processes, use as drug delivery vehicles and imaging agents for biomedical applications, and as surfaces for adsorption during removal of environmental pollutants. The use of nanoparticles in such applications has raised questions concerning their safety and impact on human health. Answers to these questions require a greater understanding of the interactions between nanoparticles and living cells. Models of the cell membrane have been employed to investigate how nanoparticles may adsorb to, fuse with, or penetrate the cell membrane, however careful consideration of the membrane model for such mechanistic studies is necessary. This thesis investigates the role of membrane lipid domains, which are lipid phase segregations comprised of saturated lipids and sterols, in modulating nanoparticle-membrane interactions and further explores how sterol chemistry impacts said interaction. Model membranes were synthesized with an equimolar ratio of sphingomyelin, 1,2-dioleoyl-sn-glycero-3-phosphocholine, and varied sterol composition to yield vesicles with varied lipid domain properties. Fluorescence anisotropy and Förster 4 resonance energy transfer of fluorescent probes was measured to quantify the degree of ordered domain formation in model vesicles. Additionally, confocal microscopy was performed to visualize lipid domains. Following lipid domain characterization, vesicles in which a self-quenching fluorescent dye was encapsulated were exposed to plain silica nanoparticles (diameter 37.5 ± 1.8 nm) and leakage of dye was measured to determine the degree of membrane disruption. By analyzing the results of vesicle leakage assays alongside the results from domain characterization, it was concluded that the lipid domain profile of the membrane alone is not an ideal predictor of nanoparticle-membrane interactions. By expanding the range of membrane models to include vesicles containing a more varied selection of sterol, it is shown that the structure of the sterol present in the membrane can impact nanoparticle-membrane interactions in a manner not predicted on the basis of the sterol’s impact on lipid domain formation. These findings help better elucidate the disruptive effects of nanomaterials on biological membranes, depending on membrane lipid chemistry and biophysical properties. 5 Dedication To my parents, Brad and Wendy, and my brother, Aaron 6 Acknowledgments I would like to acknowledge my research and thesis advisor, Dr. Amir M. Farnoud, for the mentorship he has provided to me throughout my academic career. Many of my academic goals I would not have met were it not for his guidance. Dr. Farnoud sets an excellent example for all academic mentors to strive to emulate. His enthusiasm for teaching, both in the classroom and in the lab, and his passion to always learn more inspires his peers and tutors. His charisma and genuine interest in the growth and progress of his mentees cannot be understated. My first encounter with Dr. Farnoud was as an undergraduate student taking one of several courses under his instruction. It was through knowing him in this capacity that I expressed interest to him in attending graduate school. Dr. Farnoud generously offered to accept me into his lab as a master’s student, where I have grown and learned much under his assistance. I must also acknowledge the rest of the Farnoud lab group for being supportive of each other and may we continue to support each other as we embark on whatever journey we may take in the future. Lastly, I would like to thank my committee members, Drs. Sumit Sharma, Shiyong Wu, and Douglas Goetz, who additionally is the head of the Biomedical Engineering program at Ohio University. 7 Table of Contents Page Abstract ............................................................................................................................... 3 Dedication ........................................................................................................................... 5 Acknowledgments .............................................................................................................. 6 List of Figures ..................................................................................................................... 8 Chapter 1: Introduction* .................................................................................................... 10 The Cell Membrane .................................................................................................... 11 Use of Model Membranes to Study Nanoparticle-Cell Membrane Interactions ........ 15 Objectives ................................................................................................................... 18 Chapter 2: Lipid Domain Characterization in Model Membranes ................................... 20 Introduction ................................................................................................................. 20 Materials and Methods ................................................................................................ 25 Commercial Reagents ........................................................................................... 25 Vesicle Synthesis .................................................................................................. 26 Fluorescence Anisotropy ...................................................................................... 26 Förster Resonance Energy Transfer ...................................................................... 27 Confocal Microscopy ............................................................................................ 27 Results and Discussion ............................................................................................... 28 Conclusion .................................................................................................................. 33 Chapter 3: Role of Lipid Domains and Sterol Structure in Silica Nanoparticle-Membrane Interactions ........................................................................................................................ 35 Introduction ................................................................................................................. 35 Materials and Methods ................................................................................................ 37 Commercial Reagents ........................................................................................... 37 Fluorescence Anisotropy ...................................................................................... 37 Leakage Assays ..................................................................................................... 37 Results and Discussion ............................................................................................... 40 Conclusion .................................................................................................................. 46 Chapter 4: Conclusions and Future Work ......................................................................... 47 Future Work ................................................................................................................ 49 References ......................................................................................................................... 50 8 List of Figures Page Figure 1-1. Example of phospholipid structures (left) with hydrophilic head groups shown in green and acyl chains shown in black; a saturated and unsaturated lipid are shown. Structure of cholesterol (middle). Diagram of lipid bilayer showing cholesterol packing (right). .................................................................................................................. 13 Figure 1-2. Commonly used cell membrane models. Lipid monolayer (left), supported lipid bilayer (middle), multilamellar and unilamellar vesicles in suspension (right). ...... 17 Figure 2-1. Schematic depicting fluorescence anisotropy. Light first passes the monochromator, where the proper wavelength is selected, passes through a polarizer, and strikes the sample exciting fluorophore. Light emitted from the sample passes through a set of changing horizontal and vertical polarizers, to measure the contribution of light in each plane. The emitted light passes through a second
Load more

Recommended publications
  • Bacterial Cell Membrane
    BACTERIAL CELL MEMBRANE Dr. Rakesh Sharda Department of Veterinary Microbiology NDVSU College of Veterinary Sc. & A.H., MHOW CYTOPLASMIC MEMBRANE ➢The cytoplasmic membrane, also called a cell membrane or plasma membrane, is about 7 nanometers (nm; 1/1,000,000,000 m) thick. ➢It lies internal to the cell wall and encloses the cytoplasm of the bacterium. ➢It is the most dynamic structure of a prokaryotic cell. Structure of cell membrane ➢The structure of bacterial plasma membrane is that of unit membrane, i.e., a fluid phospholipid bilayer, composed of phospholipids (40%) and peripheral and integral proteins (60%) molecules. ➢The phospholipids of bacterial cell membranes do not contain sterols as in eukaryotes, but instead consist of saturated or monounsaturated fatty acids (rarely, polyunsaturated fatty acids). ➢Many bacteria contain sterol-like molecules called hopanoids. ➢The hopanoids most likely stabilize the bacterial cytoplasmic membrane. ➢The phospholipids are amphoteric molecules with a polar hydrophilic glycerol "head" attached via an ester bond to two non-polar hydrophobic fatty acid tails. ➢The phospholipid bilayer is arranged such that the polar ends of the molecules form the outermost and innermost surface of the membrane while the non-polar ends form the center of the membrane Fluid mosaic model ➢The plasma membrane contains proteins, sugars, and other lipids in addition to the phospholipids. ➢The model that describes the arrangement of these substances in lipid bilayer is called the fluid mosaic model ➢Dispersed within the bilayer are various structural and enzymatic proteins, which carry out most membrane functions. ➢Some membrane proteins are located and function on one side or another of the membrane (peripheral proteins).
    [Show full text]
  • Organic Matter Composition Related to Methane Ebullitive Flux of an Urban Coastal Lagoon, Southeastern Brazil
    Quim. Nova, Vol. 42, No. 6, 619-627, 2019 http://dx.doi.org/10.21577/0100-4042.20170373 ORGANIC MATTER COMPOSITION RELATED TO METHANE EBULLITIVE FLUX OF AN URBAN COASTAL LAGOON, SOUTHEASTERN BRAZIL Alessandra da Fonseca Vianaa,*, , Marco Aurélio dos Santosa, Marcelo Corrêa Bernardesb and Marcelo Amorima aInstituto Alberto Luiz Coimbra de Pós-Graduação e Pesquisa de Engenharia, Universidade Federal do Rio de Janeiro, 21941-450 Rio de Janeiro – RJ, Brasil b Departamento de Geoquímica, Universidade Federal Fluminense, 24020-141 Niterói – RJ, Brasil Artigo Recebido em 25/04/2019; aceito em 04/06/2019; publicado na web em 26/06/2019 In 2016, Brazil emitted 18.25 Tg of methane. Some of these emissions occur through continental aquatic ecosystems, locations of fate and accumulation of organic and inorganic matter. Thus, the aim of this study is to evaluate the origin of organic matter in Rodrigo de Freitas Lagoon, an eutrophic, coastal and chocked lagoon in Rio de Janeiro, Brazil, through the determination of n-alkanes and sterols compounds in the upper two centimeters of sediment and compare these data with methane ebullitive flux. The concentrations of n-alkanes varied between 2.43 and 25.82 µg g-1. C29 was predominant compound in most sites, but also with important petrogenic source evidenced by the occurrence of Unresolved Complex Misture. The total concentration of sterols ranged from 2.76 to 56.01 µg g-1. β-sitostanol was the most abundant compound and coprostanol was the most relevant at the sites under -2 -1 -2 -1 influence of domestic effluents. 4CH ebullitive flux averaged 199 mg m d in the dry period and 9.3 mg m d during the wet season.
    [Show full text]
  • Study on the Derivatization Process Using NO-Bis-(Trimethylsilyl)
    World Academy of Science, Engineering and Technology International Journal of Chemical and Molecular Engineering Vol:4, No:1, 2010 Study on the Derivatization Process Using N-O-bis-(trimethylsilyl)-trifluoroacetamide, N-(tert-butyldimethylsilyl)-N-methyltrifluoroace tamide, Trimethylsilydiazomethane for the Determination of Fecal Sterols by Gas Chromatography-Mass Spectrometry Jingming Wu, Ruikang Hu, Junqi Yue, Zhaoguang Yang, and Lifeng Zhang Abstract—Fecal sterol has been proposed as a chemical indicator I. INTRODUCTION of human fecal pollution even when fecal coliform populations have O protect public health, it is important to monitor drinking diminished due to water chlorination or toxic effects of industrial effluents. This paper describes an improved derivatization procedure Twater and recreational water bodies to ensure the for simultaneous determination of four fecal sterols including pathogens are not present. Recently, various chemical coprostanol, epicholestanol, cholesterol and cholestanol using gas compounds have been used for identifying human sewage chromatography-mass spectrometry (GC-MS), via optimization study contamination in water bodies [1-3]. Coprostanol, formed on silylation procedures using N-O-bis during catabolism of cholesterol by indigenous bacteria present (trimethylsilyl)-trifluoroacetamide (BSTFA), and in the gut of humans or animals, is the primary fecal sterol N-(tert-butyldimethylsilyl)-N-methyltrifluoroacetamide (MTBSTFA), which lead to the formation of trimethylsilyl (TMS) and detected in the domestic wastewater or sediment samples [1-3]. tert-butyldimethylsilyl (TBS) derivatives, respectively. Two It has been proposed as a chemical indicator of human fecal derivatization processes of injection-port derivatization and water bath pollution even when fecal coliform populations have derivatization (60 oC, 1h) were inspected and compared.
    [Show full text]
  • Conversion of Cholesterol to Coprostanol and Cholestanol in the Estuary Sediment
    Conversion of Cholesterol to Coprostanol and Cholestanol in the Estuary Sediment 著者 "TESHIMA Shin-ichi, KANAZAWA Akio" journal or 鹿児島大学水産学部紀要=Memoirs of Faculty of publication title Fisheries Kagoshima University volume 27 number 1 page range 41-47 別言語のタイトル 海底堆積物におけるコレステロールからコプロスタ ノールおよびコレスタノールへの変換 URL http://hdl.handle.net/10232/13110 Mem. Fac. Fish., Kagoshima Univ. Vol. 27, No. 1, pp. 41-47 (1978) Conversion of Cholesterol to Coprostanol and Cholestanol in the Estuary Sediment Shin-ichi Teshima* and Akio Kanazawa* Abstract This paper deals with the conversion of cholesterol-4-14C to radioactive coprosta nol, cholestanol, and cholestenone in the estuary sediment from Kagoshima Bay, Kagoshima, Japan. The incubation of cholesterol-4-14C with the sediment and sea water gave radio active coprostanol, cholestanol, and cholestenone. The identification of these radio active compounds was performed by thin-layer chromatography and preparative gas- liquid chromatography followed by radioactive measurements. However, the incu bation of cholesterol-4-14C with sterilized sediment and with sea water (or sterilized sea water) produced extremely small amounts of the above mentioned conversion products. These results indicated that the conversion of cholesterol to coprostanol, cholestanol, and cholestenone is effected by the action of microorganisms in the sediment. Several workers have attempted to use coprostanol (5^-cholestane-3y?-ol) as an indicator of fecal pollution in water1"7*. Since the feces of human and mam mals are regarded as the only source of coprostanol in natural environments, the occurrence of coprostanol has been conceived to be indicative of water pol lution in the cause of human life. As to the marine environments, the authors have pointed out the presence of coprostanol in both sea water and the sediments in Ariake Sea, indicating that the concentration of coprostanol was markedly high in the sediments as com pared with that of sea water7).
    [Show full text]
  • Structural Basis of Sterol Recognition and Nonvesicular Transport by Lipid
    Structural basis of sterol recognition and nonvesicular PNAS PLUS transport by lipid transfer proteins anchored at membrane contact sites Junsen Tonga, Mohammad Kawsar Manika, and Young Jun Ima,1 aCollege of Pharmacy, Chonnam National University, Bukgu, Gwangju, 61186, Republic of Korea Edited by David W. Russell, University of Texas Southwestern Medical Center, Dallas, TX, and approved December 18, 2017 (received for review November 11, 2017) Membrane contact sites (MCSs) in eukaryotic cells are hotspots for roidogenic acute regulatory protein-related lipid transfer), PITP lipid exchange, which is essential for many biological functions, (phosphatidylinositol/phosphatidylcholine transfer protein), Bet_v1 including regulation of membrane properties and protein trafficking. (major pollen allergen from birch Betula verrucosa), PRELI (pro- Lipid transfer proteins anchored at membrane contact sites (LAMs) teins of relevant evolutionary and lymphoid interest), and LAMs contain sterol-specific lipid transfer domains [StARkin domain (SD)] (LTPs anchored at membrane contact sites) (9). and multiple targeting modules to specific membrane organelles. Membrane contact sites (MCSs) are closely apposed regions in Elucidating the structural mechanisms of targeting and ligand which two organellar membranes are in close proximity, typically recognition by LAMs is important for understanding the interorga- within a distance of 30 nm (7). The ER, a major site of lipid bio- nelle communication and exchange at MCSs. Here, we determined synthesis, makes contact with almost all types of subcellular or- the crystal structures of the yeast Lam6 pleckstrin homology (PH)-like ganelles (10). Oxysterol-binding proteins, which are conserved domain and the SDs of Lam2 and Lam4 in the apo form and in from yeast to humans, are suggested to have a role in the di- complex with ergosterol.
    [Show full text]
  • Evaluating Analytical Methods for Detecting Unknown Chemicals in Recycled Water
    PROJECT NO. 4992 Evaluating Analytical Methods for Detecting Unknown Chemicals in Recycled Water Evaluating Analytical Methods for Detecting Unknown Chemicals in Recycled Water Prepared by: Keith A. Maruya Charles S. Wong Southern California Coastal Water Research Project Authority 2020 The Water Research Foundation (WRF) is a nonprofit (501c3) organization which provides a unified source for One Water research and a strong presence in relationships with partner organizations, government and regulatory agencies, and Congress. The foundation conducts research in all areas of drinking water, wastewater, stormwater, and water reuse. The Water Research Foundation’s research portfolio is valued at over $700 million. The Foundation plays an important role in the translation and dissemination of applied research, technology demonstration, and education, through creation of research‐based educational tools and technology exchange opportunities. WRF serves as a leader and model for collaboration across the water industry and its materials are used to inform policymakers and the public on the science, economic value, and environmental benefits of using and recovering resources found in water, as well as the feasibility of implementing new technologies. For more information, contact: The Water Research Foundation Alexandria, VA Office Denver, CO Office 1199 North Fairfax Street, Suite 900 6666 West Quincy Avenue Alexandria, VA 22314‐1445 Denver, Colorado 80235‐3098 Tel: 571.384.2100 Tel: 303.347.6100 www.waterrf.org [email protected] ©Copyright 2020 by The Water Research Foundation. All rights reserved. Permission to copy must be obtained from The Water Research Foundation. WRF ISBN: 978‐1‐60573‐503‐0 WRF Project Number: 4992 This report was prepared by the organization(s) named below as an account of work sponsored by The Water Research Foundation.
    [Show full text]
  • Structural Evolution and Differential Effects on Lipid Bilayers
    Biophysical Journal Volume 82 March 2002 1429–1444 1429 From Lanosterol to Cholesterol: Structural Evolution and Differential Effects on Lipid Bilayers Ling Miao,* Morten Nielsen,†‡ Jenifer Thewalt,§ John H. Ipsen,† Myer Bloom,¶ Martin J. Zuckermann,§‡ and Ole G. Mouritsen* *MEMPHYS, Physics Department, University of Southern Denmark-Odense, DK-5230 Odense M, Denmark; †Department of Chemistry, Technical University of Denmark, Building 206, DK-2800 Lyngby, Denmark; ‡Centre for the Physics of Materials, Department of Physics, McGill University, Montreal, Quebec H3A 2T5, Canada; §Department of Physics, Simon Fraser University, Burnaby, V5A 1S6 British Columbia, Canada; and ¶Department of Physics and Astronomy, University of British Columbia, Vancouver, V6T 1Z3 British Columbia, Canada ABSTRACT Cholesterol is an important molecular component of the plasma membranes of mammalian cells. Its precursor in the sterol biosynthetic pathway, lanosterol, has been argued by Konrad Bloch (Bloch, K. 1965. Science. 150:19–28; 1983. CRC Crit. Rev. Biochem. 14:47–92; 1994. Blonds in Venetian Paintings, the Nine-Banded Armadillo, and Other Essays in Biochemistry. Yale University Press, New Haven, CT.) to also be a precursor in the molecular evolution of cholesterol. We present a comparative study of the effects of cholesterol and lanosterol on molecular conformational order and phase equilibria of lipid-bilayer membranes. By using deuterium NMR spectroscopy on multilamellar lipid-sterol systems in combination with Monte Carlo simulations of microscopic models of lipid-sterol interactions, we demonstrate that the evolution in the molecular chemistry from lanosterol to cholesterol is manifested in the model lipid-sterol membranes by an increase in the ability of the sterols to promote and stabilize a particular membrane phase, the liquid-ordered phase, and to induce collective order in the acyl-chain conformations of lipid molecules.
    [Show full text]
  • Mechanisms of Sterol Uptake and Transport in Yeastଝ
    G Model SBMB-3587; No. of Pages 9 ARTICLE IN PRESS Journal of Steroid Biochemistry & Molecular Biology xxx (2010) xxx–xxx Contents lists available at ScienceDirect Journal of Steroid Biochemistry and Molecular Biology journal homepage: www.elsevier.com/locate/jsbmb Review Mechanisms of sterol uptake and transport in yeastଝ Nicolas Jacquier, Roger Schneiter ∗ Department of Medicine, Division of Biochemistry, University of Fribourg, Chemin du Musée 5, CH-1700 Fribourg, Switzerland article info abstract Article history: Sterols are essential lipid components of eukaryotic membranes. Here we summarize recent advances in Received 12 July 2010 understanding how sterols are transported between different membranes. Baker’s yeast is a particularly Received in revised form attractive organism to dissect this lipid transport pathway, because cells can synthesize their own major 12 November 2010 sterol, ergosterol, in the membrane of the endoplasmic reticulum from where it is then transported to Accepted 30 November 2010 the plasma membrane. However, Saccharomyces cerevisiae is also a facultative anaerobic organism, which becomes sterol auxotroph in the absence of oxygen. Under these conditions, cells take up sterol from the Keywords: environment and transport the lipid back into the membrane of the endoplasmic reticulum, where the Cholesterol Sterol metabolism free sterol becomes esterified and is then stored in lipid droplets. Steryl ester formation is thus a reliable Lipid homeostasis readout to assess the back-transport of exogenously provided sterols from the plasma membrane to the Lipid transport endoplasmic reticulum. Structure/function analysis has revealed that the bulk membrane function of Endoplasmic reticulum the fungal ergosterol can be provided by structurally related sterols, including the mammalian choles- Lipid detoxification terol.
    [Show full text]
  • View Data Sheet
    PRODUCT DATA SHEET Coprostanol Catalog number: 1116, 1116-k Molecular Formula: C 27 H48 O Common Name: 5-beta -Cholestane-3-beta -ol Molecular Weight: 389 Source: semisynthetic Storage: -20°C Solubility: chloroform, ethyl ether, warm, Purity: TLC >98% methanol TLC System: hexane/ethyl ether, (85:15 by vol) CAS number: 360-68-9 Appearance: solid H H H HO H Application Notes: Coprostanol is formed via the biohydrogentaion of cholesterol in many animals by intestinal bacteria. It is widely used as a biomarker for human fecal matter in the environment, especially in regards to sewage pollution of water sources. 1 Coprostanol can be converted to coprostanone, another important fecal biomarker. Whereas many sterols are found esterified in vivo rather than as free sterols, coprostanol is not usually found esterified and is absorbed through the intestine as a free sterol. 2 After absorption through the intestine a small amount of coprostanol is converted to acidic, neutral, and water soluble compounds. 3 This product is a high purity sterol that is ideal as an analytical standard. 4 Selected References: 1. P. Nichols et al. “Comparison of the abundance of the fecal sterol coprostanol and fecal bacterial groups in inner-shelf waters and sediments near Sydney, Australia” Journal of Chromatography A , vol. 643(1-2) pp. 189-195, 1993 2. R. Rosenfeld, B. Zumoff, and L. Hellman “Metabolism of coprostanol-C14 and cholestanol-4-C14 in man” Journal of Lipid Research , vol. 4(3) pp. 337- 340, 1963 3. R. Bell et al. “Bile Acids” Journal of Biological Chemistry , vol. 240(3) pp.
    [Show full text]
  • A Critical Review of Synthetic Chemicals in Surface Waters of the US, the EU and China
    Environment International 131 (2019) 104994 Contents lists available at ScienceDirect Environment International journal homepage: www.elsevier.com/locate/envint Review article A critical review of synthetic chemicals in surface waters of the US, the EU T and China ⁎ Wendi Fanga, Ying Penga, Derek Muirb,c, Jun Lind, Xiaowei Zhanga, a State Key Laboratory of Pollution Control & Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023, PR China b Environment and Climate Change Canada, Canada Centre for Inland Waters, 867 Lakeshore Road, Burlington, ON L7S 1A1, Canada c School of Environment, Jinan University, Guangzhou, PR China d Solid Waste and Chemicals Management Center, Ministry of Ecology and Environment, PR China ARTICLE INFO ABSTRACT Handling editor: Adrian Covaci There is a wide concern that emerging organic pollutants (EOPs) in surface water could adversely affect human Keywords: health and wildlife. However, the geographic distribution, exposure pattern and ecological risk of emerging Chemical pollution organic pollutants are poorly understood at a global scale. This paper provides a comprehensive survey on the Risk assessment exposure level of EOPs in China, the US and the EU based on the published literature. The hazard level of three Pesticide categories of EOPs, namely pharmaceuticals and personal care products (PPCPs), pesticides and industrial Industry chemicals was further evaluated by adopting a novel Aquatic HazPi index that jointly accounts for the persis- Pharmaceutical and personal care products tence, bioaccumulation, toxicity and bioactivity. Furthermore, a correlation analysis of land use with the surface Land use water exposure status regarding the synthetic chemicals was conducted. According to the published data re- ported between 2010 and 2016, the concentration of pesticides in the US was higher than in the EU and China.
    [Show full text]
  • The Antifungal Mechanism of Amphotericin B Elucidated in Ergosterol and Cholesterol-Containing Membranes Using Neutron Reflectometry
    nanomaterials Article The Antifungal Mechanism of Amphotericin B Elucidated in Ergosterol and Cholesterol-Containing Membranes Using Neutron Reflectometry Robin Delhom 1,2,3 , Andrew Nelson 4 , Valerie Laux 1, Michael Haertlein 1, Wolfgang Knecht 3,5, Giovanna Fragneto 1 and Hanna P. Wacklin-Knecht 2,6,* 1 Institut Laue-Langevin, 71 Avenue des Martyrs, CS 20156, 38042 Grenoble CEDEX 9, France; [email protected] (R.D.); [email protected] (V.L.); [email protected] (M.H.); [email protected] (G.F.) 2 European Spallation Source ERIC, P.O. Box 176, 22100 Lund, Sweden 3 Department of Biology, Lund University, Sölvegatan 35, 22362 Lund, Sweden; [email protected] 4 Australian Centre for Neutron Scattering, Australian Nuclear Science and Technology Organization, Locked Bag 2001, Kirrawee DC, NSW 2232, Australia; [email protected] 5 Lund Protein Production Platform, Lund University, Sölvegatan 35, 22362 Lund, Sweden 6 Department of Chemistry, Division of Physical Chemistry, Lund University, P.O. Box 124, 22100 Lund, Sweden * Correspondence: [email protected] Received: 10 November 2020; Accepted: 4 December 2020; Published: 6 December 2020 Abstract: We have characterized and compared the structures of ergosterol- and cholesterol-containing 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) membranes before and after interaction with the amphiphilic antifungal drug amphotericin B (AmB) using neutron reflection. AmB inserts into both pure POPC and sterol-containing membranes in the lipid chain region and does not significantly perturb the structure of pure POPC membranes. By selective per-deuteration of the lipids/sterols, we show that AmB extracts ergosterol but not cholesterol from the bilayers and inserts to a much higher degree in the cholesterol-containing membranes.
    [Show full text]
  • Sflifttrru$&FV
    Summary 547 Aspirin blocks the qmthesis of prostaglandins that induce pain and fever. It also has been reported that low doses of aspirin reduce the danger of heart attack and stroke by blocking the synthesis of prostaglandins that promote blood clotting. Aspirin's inhibition of the formation of these prostaglandins accounts for its effectivenessas an analgesic (pain killer), antipyretic (fever killer), and anticlotting agent. Leukotrienes are another classof hormone-like substancessynthesized from arachidonic acid. Lettkotriene Bn and leukotriene En are examples of leukotrienes. Unlike the prostaglandins, the leukotrienes contain three car- bon-carbon double bonds in a row in their molecular structures. I NHz Leukotriene Ea Certain leukotrienes constitute what is referred to as the slow-acting sub- stances of anaphylactic shock. Anaphylactic shock is a drastic allergic responseof the body that can be fatal. Severeallergies to foods such as shellfish or peanuts can trigger anaphylactic shock in susceptible people. The symptoms of anaphylactic shock include closing of the throat, blocking the airways. Heart stoppage also can occur, leading to death. Leukotrienes are also implicated in less severeallergic reactions, asthma, inflammations, and heart attacks. Recent studies suggestthat dietary fish oils can reduce levels of leukotrienes and reduce the risk of heart attack. sflifttrru$&FV Lipids are a broad class of naturally occurring, rela- mon glycolipids. Phospholipid and glycolipid mole- tively water-insoluble molecules. Triglycerides-tri- cules have polar heads and hydrophobic tails. The esters of glycerol and fatty acids-are the most lipid bilayer is the fundamental structure of lipo- abundant lipids in animal tissue. somes and the membranes of cells and organelles.
    [Show full text]