Introduction to Membranes - Cell Biology 1 PDF

4/1/24 Introduction, Membranes Cell Biology 1 Xuan-Hung Nguyen, Ph.D Hi-Tech Center Vinmec Healthcare System 1 Outlines Plasma membr...

4/1/24 Introduction, Membranes Cell Biology 1 Xuan-Hung Nguyen, Ph.D Hi-Tech Center Vinmec Healthcare System 1 Outlines Plasma membrane ENDOMEMBRANE SYSTEM HEADQUATER ER Nucleus Golgi apparatus 01 04 Vesicles DIGESTION CENTER 02 03 POWER PLAN Lysosome Mitochondria Peroxisome Chloroplast Vacuole 2 1  4/1/24 E /S/C /I Phospholipids Carbohydrates P G lycerol Cholesterols Proteins Fatty acid tail Fatty ac Compartment Barrier id tail Sphingolipids E P Sugar Transport NH Communication Fatty acid tail Sphi ngos support/ motility (3) Membrane (1) Membrane (2) Membrane ine structure functions transport CELL MEMBRANE (4) Membrane (5) Membrane (6) Membrane channel carriers pumps Open Gated +++ +++ PS _ _ --- --- P-type V-type PS proton +++ +++ ABC F-type Voltage Ligand Mechanical transporter ATP synthase 3 WHAT ARE PLASMA MEMBRANE FUNCTIONS? Carbohydrates Protein 1. Barrier: Separate the cell from the outside 2. Exchange: Control intracellular vs extracellular Phospholipids environment. Transporters Functions Carriers Channels 3. Communicate: with outside environment and other cells. 3. Communication 1. Physical & Receptor proteins Electrical barrier Adhesion proteins hold tissues together and directly communicate between cells 4. Structure support & cell motility. 4. Structural support 2. Exchange with and cell motility environment https://www.mechanobio.info/membrane-dynamics/ 4 2  4/1/24 MEMBRANES There would not be cells without membranes. small and flexible to fit through smallest blood vessels Properties: fluid layers, semipermeable, flexible, continuous molecular turnover s c e ll How can the cell membrane carry out such diverse functions? her h ot or eac ns t e n s io xt ge lo n Silverthorn et al. 2019. Human physiology: an integrated approach. 8th. Pearson Milo et al. Cell Biology by the Numbers. 2016 5 Membranes- Physical and Electrical barrier Cell membrane (50% mass) is made of lipids © 2013 OpenStax, Creative Commons License. Access for free at https://openstax.org/books/anatomy-and-physiology/pages/1-introduction 6 3  4/1/24 PHOSPHOLIPIDS Phospholipids: most abundant membrane lipids Head end: H2O - phosphate esterified with the hydroxyl group of H2O alcohols such as choline, serine, ethanolamine or inositol. H2O - hydrophilic and faces the water side in the lipid bilayer Hydrophobic tail: - long chain fatty acids - align in the middle of the bilayer. H2O - > 50% of fatty acids in membranes have one or H2O more double bonds H2O Biological membranes contain > 100 types of phospholipids © 2013 OpenStax, Creative Commons License. Access for free at https://openstax.org/books/anatomy-and-physiology/pages/1-introduction 7 PHOSPHOLIPIDS BILAYER Measure surface area Gorter and Grendel, 1925 Why RBCs had been used? ns io ct t ra ex id L ip Stationary Movable barrier barrier Lipids M ea Red blood cells su re su r fa ce ar ea 5 × 106 lipid molecules / 1 μm × 1 μm area of lipid bilayer 109 lipid molecules / plasma membrane of a small animal cell Ratio comarison Cell and Molecular Biology. 4e. 2005. John Wiley & Sons 8 4  4/1/24 PHOSPHOLIPID BILAYER Lipid micelles Lipid bilayers Lipid bilayer can self-assemble in water, into particles or sheets Micelles: short tails phospholipids Bilayers: longer tails phospholipids No input of energy is required Liposomes: larger double layer spheres with inner water- containing core, for drug/DNA/RNA delivery Deliver to specific cell Caelyx: liposome containing chemotherapy drug doxorubicin, approved for metastatic breast cancer treatment mRNA vaccine © 2007 Wikimedia Commons, Creative Commons License, User: LadyofHats; Gerald Karp, Janet Iwasa, Wallace Marshall. 2016. Karp’s Cell and Molecular Biology. 8th. Wiley John Wiley & Sons 9 PHYSICAL BARRIER Hydrocarbon chain affects the lipid bilayer characteristics by: H2O (1) Number of double bonds: a double bond H2O between carbon atoms produces a “kink” in H2O an otherwise straight hydrocarbon chain (2) Length: the longer the stiffer and lesser permeable H2O H2O H2O © 2013 OpenStax, Creative Commons License. Access for free at https://openstax.org/books/anatomy-and-physiology/pages/1-introduction 10 5  4/1/24 QUESTIONS The structure of a lipid bilayer is determined by the particular properties of its lipid molecules. What would happen if the hydrocarbon tails were shorter than normal, say, about 10 carbon atoms long? A. You would have a more stable lipid bilayer B. You would have a less fluid lipid bilayer C. You would have a more fluid lipid bilayer D. You would have unchanged membrane fluidity Lipid bilayers would be much more fluid, as the tails would have less tendency to interact with one another. The bilayers would also be less stable, as the shorter hydrocarbon tails would be less hydrophobic, so the forces that drive the formation of the bilayer would be reduced. 11 QUESTIONS The structure of a lipid bilayer is determined by the particular properties of its lipid molecules. What would happen if all of the hydrocarbon tails were unsaturated? A. You would have a more stable lipid bilayer B. You would have a less fluid lipid bilayer C. You would have a much more fluid lipid bilayer D. You would have unchanged membrane fluidity the saturated lipid molecules would tend to aggregate with one another because they can pack so much more tightly and would therefore form patches of much-reduced fluidity. 12 6  4/1/24 MEMBRANE COMPOENTS Silverthorn et al. 2019. Human physiology: an integrated approach. 8th. Pearson 13 SPHINGOLIPIDS Sphingosine: a nitrogen-containing base made Sphingosine from serine and a long chain fatty acid. Sphingomyelin: esterify the head of sphingosine with phosphorylcholine or phosphoethanolamine Glycosphingolipids: esterify the head of sphingosine with sugars (cerebrosides or involved in the regulation of cell gangliosides) growth, differentiation, and apoptosis Sphingolipids: ü more abundant in cell membranes than other membranes. ü maintain the structural integrity and fluidity involved in cell- cell recognition, of the membrane adhesion, lipid raft formation ü play a role in cell signaling pathways Prominent in neurons R: fatty acid chain Karp et al., Karp’s Cell and molecular biology. 2016. Willey 14 7  4/1/24 CHOLESTEROL ASYMMETRICAL DISTRIBUTION OF LIPIDS Cholesterol: hydrophobic and insert between the hydrophilic heads of phospholipids. Steroid rings in cholesterol are bulky à increase the density of the hydrophobic section à reduced the permeability Lipid raft: association of cholesterol and sphingolipids to form “rafts” within the outer layer. SM: Sphingomyelin; GS, glycosphingolipid; PC, phosphatidylcholine; PE, phosphatidylethanolamine; PS, phosphatidylserine Pollard et al., 2017. Cell Biology, 3rd 15 MEMBRANE COMPOENTS Silverthorn et al. 2019. Human physiology: an integrated approach. 8th. Pearson 16 8  4/1/24 CARBOHYDRATE CHAINS Textbook reference: Chapter 13 Glycoprotein Membrane carbohydrates: usually short, branched chains of < 15 sugar units Carbohydrate chain Outer leaflet: contains many glycoproteins protrude outside the cell. Receptors on other cell membranes, Polypeptide chain adhesion molecules and growth factors recognize and bind to the carbohydrate chains of PM glycoproteins. - ABO blood types: differences in glycoprotein carbohydrate chains. PM glycoproteins are important for cell- cell communication and adhesion. 2008, Public Domain, WikiMedia Commons, Author: Kosigrim 2014, Public Domain, WikiMedia Commons, Author: Delphi234 17 PHYSICAL AND ELECTRICAL BARRIER Lipid bilayer: permeability barrier to most water- soluble molecules Channels or transporters: transport ionic and hydrophilic molecules cross membranes à electrical barrier Aquaporin channels: allow water to cross - Driven by osmotic forces - Solute concentration Lipid soluble molecules can diffuse across most membranes. Proteins cannot cross cell membranes. Mader and Windelspecht. Human Biology. 5th. 2018. McGraw-Hill Education 18 9  4/1/24 REAL WORLD CASES_NO1 In 1992, the medical personnel at isolated Atoifi Hospital in the Solomon Islands of the South Pacific were faced with a dilemma. A patient was vomiting and needed intravenous (IV) fluids, but the hospital’s supply had run out, and it would be several days before a plane could bring more. Intravenous fluids (usually shortened to 'IV' fluids) are liquids given to replace water, sugar and salt that you might need if you are ill or having an operation, and can't eat or drink as you would normally What would you do this case? 19 REAL WORLD CASES_NO1 Solution: make an IV of coconut water, the sterile solution that forms in the hollow center of developing coconuts. For 2 days, the patient received a slow drip of fluid into his veins directly from young coconuts suspended next to his bed. He soon recovered and was well enough to go home. 20 10  4/1/24 MEMBRANE COMPOENTS Silverthorn et al. 2019. Human physiology: an integrated approach. 8th. Pearson 21 Membranes- Structural support and cell motility For mammalian cells, major changes in cell shape are evident in processes that include cell spreading, migration, and cell division as well as differentiation and death. 22 11  4/1/24 PLASMA MEMBRANE STRUCTURE The plasma membrane (PM) is a fluid, flexible structure. PMs are thicker and richer in sphingolipids (10%) and cholesterol (35%) than membranes of intracellular organelles. Fibers of extracellular matrix (ECM) Sphingolipids and cholesterol associate with each other to form collections called rafts. Glycoprotein Carbohydrate 7-10 nm: a stack of more than 8,000 plasma membranes to equal the thickness of a paper Glycolipid Phospholipid Proteins Cholesterol Microfilaments of cytoskeleton Pollard et al., 2017. Cell Biology, 3rd; Sezgin et al., 2017; Urry et al., Campbell Biology. 2020. Pearson 23 DIVERSITY OF MEMBRANE SHAPES Development of various human blood cells Stem cells (SCs) near the osteoblasts undergo asymmetric division SCs far the osteoblast divide symmetrically SCs differentiate into three different lineages erythroblasts - Megakaryocytes (MKs) undergo fragmentation into platelets. - Macrophages phagocytose the nuclei, leading to enucleated red blood cells (RBCs) - White blood cells (WBCs) can spread, migrate and bind Discher. 2018. Biomembrane Mechanical Properties Direct Diverse Cell Functions 24 12  4/1/24 MAJOR PHOSPHOLIPIDS IN MAMMALIAN PM Inositol Ethanolamine Serine Choline Choline PE PI PS & PC P P NH Glycerol PI à inverted conical Fatty acid tail Sp h Fatty acid tail ing Fatty a PE: smaller polar head à conical shape osin e cid PS & PC: cylindrical lipids à flat monolayer tai l Phosphatidyl Phosphatidyl Phosphatidyl Phosphatidyl Sphingomyelin -inositol -ethanolamine -serine -choline PI PE PS PC SM phosphoglycerides 26 https://www.youtube.com/watch?v=gDb8ENGOrvw 27 13  4/1/24 LIPIDS DISTRIBUTION IN EUKARYOTE MEMBRANES Lipid composition can determine the physical state of the membrane and influence the activity of particular membrane proteins PC: phosphatidylcholine PS: phosphatidylserine PE: phosphatidylethanolamine PI: phosphatydilinositol PS: phosphatidylserine SM: sphingomyelin ISL: inositol sphingolipid CL: cardiolipin MBP: bis monoacylglycerol phosphate https://mmegias.webs.uvigo.es/02-english/5-celulas/3-lipidos.php 30 QUESTIONS Predict which one of the following organisms will have the highest percentage of unsaturated phospholipids in its membranes. Explain your answer. A. Antarctic fish C. Polar bear B. Desert snake D. Thermophilic bacterium that lives in hot springs at 100oC 31 14  4/1/24 Membranes- exchange with the environment The cell membrane controls the entry of ions and nutrients into the cell, the elimination of cellular wastes, and the release of products from the cell. 32 MEMBRANE TRANSPORT Lipid bilayer: maintains concentrations of solutes in cytosol that differ from those in the extracellular fluid and in each organelles. Cells evolve ways of transferring specific water- soluble molecules and ions across their membranes in order to ingest essential nutrients, excrete metabolic waste products, and regulate intracellular ion concentrations Mader and Windelspecht. Human Biology. 5th. 2018. McGraw-Hill Education 33 15  4/1/24 MECHANISMS OF CROSSING MEMBRANE Silverthorn et al. 2019. Human physiology: an integrated approach. 8th. Pearson 34 4 BASIC MECHANISMS OF CROSSING MEMBRANE (1) Passive-Simple diffusion: always from high to low (1) (2) (3) (4) O2 Na+ Glucose K+ concentration. (2) Passive-channel diffusion: through aqueous channel that provide openings in the membrane that let specific substances through. (3) Passive-Facilitated diffusion/cotransport: carrier/transporter binds specifically to solute molecules, change shape à move the solutes across the membrane, always from high to low concentration. Specificity 10-20X Intermediate Absolute (4) Active transport: protein transporter (pump), use Rate (ion/sec) 106