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Cell Membrane: Structure and Function Assoc. Prof. Dr. Onur Baykara 1 Cell Membrane Structure  All living cells are surrounded by a membrane.  A cell membrane is also known as plasma membrane. 2 Functions of the (Cell) Plasma Membrane • Contains the cytoplasm (fluid in cell) • Acts as a p...

Cell Membrane: Structure and Function Assoc. Prof. Dr. Onur Baykara 1 Cell Membrane Structure  All living cells are surrounded by a membrane.  A cell membrane is also known as plasma membrane. 2 Functions of the (Cell) Plasma Membrane • Contains the cytoplasm (fluid in cell) • Acts as a protective and selective barrier against foreign substances • Regulates transportation of molecules and filters what goes in & out of cell • Allows cell-cell recognition and interaction • Provides a binding site for enzymes (proteins) and hormones, therefore responds to signals coming out of the cell, such as proliferation, growth, apoptosis, etc. • Provides anchoring sites for filaments of cytoskeleton (for forming tissues and organs) (Further lessons) • Interlocking surfaces bind cells together for 3 Structure of Cell Membrane Phospholipids Proteins (peripheral and integral) Cholesterol Carbohydrates 4 Membrane lipids • Lipids are a diverse and broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others • The term "lipid" is sometimes used as a synonym for fats, but fats are a subgroup of lipids called triglycerides • Three major classes of membrane lipids • Phospholipids • Glycolipids • Cholesterol • Lipids are amphiphilic: they have one end that is soluble in water ('polar') and an ending that is soluble in fat ('nonpolar') 5 WHAT ARE PHOSPHOLIPIDS? If a lipid carries a phosphate, it is called a phospholipid Phospholipids are important structural components of cell membranes. Phospholipids are modified so that a phosphate group (PO-4) replaces one of the three fatty acids normally found on a lipid. Lipid They are synthesized in the cytosolic side of ER membrane The phosphate group can be modified with simple organic molecules such as choline, ethanolamine or serine The addition of this group makes one polar "head" and two 6 HYDROPHILIC HEAD At one end of the phospholipid is a phosphate group and several double bonded oxygens. The electrons at this end of the molecule are not shared equally. This end of the molecule has a charge and is attracted to water. It is POLAR HYDROPHOBIC TAILS The two long chains coming off of the bottom of this molecule are made up of carbon and hydrogen. Because both of these elements share their electrons evenly, these chains have no charge. They are NON POLAR. Molecules with no charge are not attracted to water; as a result water molecules tend to push them out of the way as they are attracted to each other. This causes molecules with no charge not to dissolve in water. 7 Phospholipids can form: BILAYERS -2 layers of phospholipids with hydrophobic tails are protected inside by the hydrophilic heads. The PHOSPHOLIPID BILAYER is the basic structure of membranes. 8 Polar heads are hydrophilic “water loving” Nonpolar tails are hydrophobic “water fearing” Phospholipids make membranes Selectively Permeable- able to control what crosses 9 Polar, Hydrophilic “head” Nonpolar, Hydrophobic Fatty acid “tails” Polar, Hydrophilic “head” 10 Cholesterol • A class of lipids, produced in liver and intestines • A type of sterol (or modified steroid) • All animal cells synthesize it and it is an essential component of cell membranes • Serves as a precursor for the biosynthesis of steroid hormones, bile acid and vitamin D • A 70 kg person has approx. 35-40 gr cholesterol in body, mostly found in cell membrane (30-50% of membrane) • Builds and maintains membranes and modulates membrane fluidity through temperature fluctations • Gives mechanical stability • Helps to prevent ions from passing through the membrane. • Familial hypercholesterolemia/genes (LDLR, APOB, PCSK9) 11 FLUID MOSAIC MODEL (Singer and Nicholson model) Cell membranes also contain proteins within the phospholipid bilayer. This ‘model’ for the structure of the membrane is called the: FLUID MOSAIC MODEL FLUID- because individual phospholipids and proteins can move around freely within the layer, like it’s a liquid. MOSAIC- because of the pattern produced by the scattered protein molecules when the membrane is viewed from 12 The fluid mosaic model was developed using Freeze Fracture Studies. The fracture occurs between the two phospholipid layers. You can clearly see the exposed proteins sticking out of the two layers. Individual phospholipids are too small to see. MOSAIC 13 Fluidity of lipid membranes • Lateral • Rotational • Flip-flop • Flippases move phospholipids from the outer leaflet to the inner leaflet. • Floppases move phospholipids in the opposite direction, particularly the choline derived phospholipids phospatidylcholine and sphingomyelin. Floppases also mediate cholesterol transport from the intracellular monolayer to the extracellular monolayer. • Scramblases exchange phospholipids between the two leaflets in a calcium activated, ATP-independent process. 14 Proteins Are Critical to Membrane Function 15 Functions of membrane proteins • Membrane receptor proteins relay signals between the cell's internal and external environments. • Transport proteins move molecules and ions across the membrane. • Membrane enzymes may have many activities, such as oxidoreductase, transferase or hydrolase. • Cell adhesion molecules allow cells to identify each other and interact. For example, proteins involved in immune response • Membrane proteins are the targets of over 50% of all modern medicinal drugs 16 Proteins can float in the membrane or be fixed and also have hydrophobic and hydrophilic portions. Proteins may be embedded in the outer layer or in the inner layer (peripheral proteins) and some span the two layers (integral-transmembrane proteins). Hydrophobic and Hydrophilic parts of the protein molecules sit next to the Hydrophobic and Hydrophilic portions of the phospholipids of the membrane. This ensures the proteins stay in the membrane. About a third of all human proteins are membrane proteins, and these are targets for more than half of all drugs 17 • Integral membrane proteins • Act as receptors on the membrane surface • Channels or carriers involved in ion and solute movement • Agents that transfer electrons during photosynthesis and respiration. • Peripheral transmembrane proteins • Provide mechanical support to membrane • Act as a retainer for the integral membrane • Other peripheral proteins on the surface of the inner plasma membrane act as enzymes or factors that transmit transmembrane signals. • Peripheral proteins typically • Lipid anchored proteins have a dynamic relationship • Numerous proteins on the outer surface themembrane plasma membrane withofthe are anchored to the membrane by a small, complex oligosaccharide attached to the phosphatidylinositol molecule embedded in the outer leaves of the lipid bilayer. Peripheral membrane proteins containing this type of glycosyl phosphatidylinositol (GPI) link are called “GPI-associated proteins” 18 Carbohydrates • The third major component of plasma membranes. • In general, they are found on the outside surface of cells and are bound either to proteins (forming glycoproteins) or to lipids (forming glycolipids). • These carbohydrate chains may consist of 260 monosaccharide units and can be either straight or branched. • Along with membrane proteins, these carbohydrates form distinctive cellular markers, sort of like molecular ID badges, that allow cells to recognize each other. • These markers are very important in the immune system, allowing immune cells to differentiate between body cells, which they shouldn’t attack, and foreign cells or tissues, which they should. 19 Glycoproteins Some of the proteins have carbohydrates attached to them – (surface carbohydrates) GLYCOPROTEINS. Glycoproteins act as chemical id tags. Blood types are the result different glycoproteins. 20 Glycolipid s • Glycolipids are lipids with a carbohydrate attached by a glycosidic (covalent) bond. • They maintain the stability of the cell membrane and facilitate cellular recognition (crucial to the immune response and for connections between the cells that connect to one another to form tissues). 21 Cell Membrane Permeability Hydrophobic pass easily Hydrophilic DO NOT 22 Semipermeable Membrane Small molecules and larger non-polar molecules move through easily. e.g. O2, CO2, H2O 23 Semipermeable Membrane Ions Hydrophilic molecules larger than water Large molecules such as proteins do not move through the membrane on their own. 24 Types of Transport Across Cell Membranes • Passive transport Simple diffusion Facilitated diffusion • Active transport 25 Two Forms of Transport Across the Membrane 26 Passive Transport Simple Diffusion Doesn’t require cell energy Molecules move from high to low concentration Example: Oxygen or water diffusing into a cell and carbon dioxide diffusing out. out 27 Passive Transport Molecules move from HIGH concentration to LOW concentration, down their concentration gradient. 28 Diffusion is a PASSIVE process which means no cell energy is used to make the molecules move, they have a natural KINETIC ENERGY 29 Diffusion of Liquids 30 Diffusion through a membrane Cell membrane Solute moves DOWN the concentration gradient from HIGH to LOW concentration 31 Osmosis-Diffusion of H2O Across A Moves from HIGH water potential (low solute) to LOW water potential Membrane (high solute) Low solute High solute concentration concentration 32 Diffusion vs Osmosis • In DIFFUSION, MATERIALS/MOLECULES move from high concentration to low contration (like perfume diffusing into a room) • In OSMOSIS, WATER MOLECULES move from high concentration to low contration 33 10% NaCL 90% H2O ENVIRONMENT CELL 10% NaCL 90% H2O NO NET MOVEMENT What is the direction of water movement? The cell is atequilibrium _______________. 34 10% NaCL 90% H2O CELL 20% NaCL 80% H2O What is the direction of water movement? 35 15% NaCL 85% H2O ENVIRONMENT CELL 5% NaCL 95% H2O What is the direction of water movement? 36 Hippopotam us Cells in Solutions 37 Isotonic Solution Hypotonic Solution Hypertonic Solution NO NET MOVEMENT OF H2O (equal amounts entering & leaving) CYTOLYSIS (water diffuses into the cell) CRENATION (water diffuses out of the cell) 38 Cytolysis & Crenation Cytolysis Crenatio 39 Osmosis in Red Blood Cells In Isotonic Solution In Hypotonic Solution In Hypertonic Solution 40 Transport Proteins Channel proteins are embedded in the cell membrane & have a pore for materials to cross Carrier proteins can change shape to move material from one side of the membrane to the other 41 Passive Transport Facilitated Diffusion Doesn’t require energy Uses transport proteins to move high to low concentration Moves materials with the concentration gradient. Examples: Glucose or amino acids moving from blood into a cell. 42 Facilitated Diffusion Molecules will randomly move through the pores in Channel Proteins. 43 Facilitated Diffusion  Some Carrier proteins do not extend through the membrane.  They bond and drag molecules through the lipid bilayer and release them on the opposite side. 44 Carrier Proteins  Other carrier proteins change shape to move materials across the cell 45 Active Transport Requires energy or ATP Moves materials from LOW to HIGH concentration AGAINST concentration gradient 46 Active Transport Examples:  Pumping Na+ (sodium ions) out and K+ (potassium ions) in against strong concentration gradients.  Called Na+-K+ Pump  (Keeps cell 47 Sodium-Potassium Pump (+ ) (-) 3 Na+ pumped out for every 2 K+ pumped in; creates a membrane 48 49 Moving the “Big Stuff” Out Exocytosi s- moving things out. Molecules are moved out of the cell by vesicles that fuse with the plasma membrane. This is how many hormones are secreted and how nerve cells communicate with one another. another 50 Exocytosis Large molecules that are manufactured in the cell are released through the cell membrane. Inside Cell Cell environment 51 Exocytosis Exocytic vesicle immediately after fusion with plasma membrane. 52 Moving the “Big Stuff”move In materials into the cell by Large molecules one of three forms of endocytosis. endocytosis 1.Pinocytosis 2.Receptor-mediated Endocytosis 3.Phagocytosis 53 1. Pinocytosis ost common form of endocytosis. endocytosis Takes in dissolved molecules as a 54 Pinocytosis  Cell forms an invagination  Materials dissolved in water are brought into cell  Called “Cell Drinking” 55 Example of Pinocytosis pinocytic vesicles forming mature transport vesicle Transport across a capillary cell (blue). 56 2. Receptor-Mediated Endocytosi Some integral proteins have receptors on their surface to recognize & take in hormones, 57 Receptor-Mediated Endocytosis Coated pit Vesicle 58 3. Phagocytosis Used to engulf large particles such as food, bacteria, etc. into vesicles Called “Cell Eating” 59 Cell membrane differentiations • The cell membrane differentiates according to its functions on the apical, lateral and basal surfaces of the cell. • Apical, that is, free surface differentiation Microvilli, cilia and stereocilia. • Lateral surface differentiations are called junctional complexes. Tight junctions, Anchoring junctions, Communication (channel forming) connections (e.g. gap connections). • Basal lamina can be given as an example of basal surface differentiation. 60 Lateral membrane differentiations Microvillu s Tight junction (Zonula occludens) / actin filaments Adherens junction (Zonula adherens) / actin filaments Desmoso me (Macula occludens) / intermediate filaments Gap junction Hemidesmoso me Basal lamina Uses adapters intermediate filaments Apical membrane differentiations • Microvillus is cytoplasmic membran folding that increases surface absorption area • Mostly found on epithelial cells (e.g intestinal cells) • Contains actin filaments • Cilia is a motile membrane differentiation • Composed of 9 double and 2 single microtubules made of α and β tubulins, moves by sliding • Helps carry the secretory molecules in epithelial cells, transport of foreign substances and sperm’s whiplash movement • Excretion of mucus and in trachea epithelium, transfers sperm from ductus efferens to ductus epididymis and transfers oocyte from tuba uterina epithelium to uterus • Stereocilia(stereovillus), contains actin filaments. Increases absorption area. Found in hair cell receptors in inner ear. Its loss causes deafness Microvillus Cilia Stereocilia 62 Lateral membrane differentiations Types of junctions and communications • Tight junctions (zonula occludens)-connects cells through actin filaments (uses adaptör molecules such as occludin and claudin, selectively permits molecules. e.g. Prevents passage of digestive enzymes from lumen to blood in pancreatic asinus cells, OR prevents toxins in kidney distal tubule to pass to blood AND functions in blood brain barrier • Anchoring junctions Adherens junctions (zonula adherens)-Link one cell to another through actin filament (Many types of cells) (uses cadherins, nectins, etc.) Desmosomes (macula adherens)-Link one cell to another through intermediate filaments (Many types of cells, provides tissue integrity against damage and abrasion, uses desmosomal cadherins, desmogleins, desmocollins) Hemidesmosomes-Link cells to the matrix through intermediate filaments (Restricted to epithelial cells, uses integrins and provides integrity) Cell-matrix adhesion complexes (many types of cells and cell migration in motile cells) • Gap junctions (intercellular connection through adapters (connexons), cell to cell connection Basal lamina differentiations • The structure that provides physical support to the cells as a thin extracellular matrix layer in the basal regions of the epithelial cells is called the basal lamina • Acts as a selective molecular filter, enclosing not only epithelial cells but also muscle, fat, and Schwann cells, separating cells from connective tissue. • Controls cell viability, proliferation, differentiation and migration • Forms microenvironment during embryonic development 64

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