Structure and Function of Cellular Membranes PDF

Structure and function of cellular membranes Asst. Prof. Samet UÇAK Dept. of Medical Biology and Genetics 1 Cellular Components I-Nucleus II-Cytoplasm Cytoplasm; 1-Cell Organelles 2-Cytoskeleton 3-Cellular Inclusions 2 ...

Structure and function of cellular membranes Asst. Prof. Samet UÇAK Dept. of Medical Biology and Genetics 1 Cellular Components I-Nucleus II-Cytoplasm Cytoplasm; 1-Cell Organelles 2-Cytoskeleton 3-Cellular Inclusions 2  Organelles (Living components, responsible for cellular functions, permanent structures) Mitochondria Endoplasmic reticulum (RER,SER) Ribosome Golgi Complex Lysosome Peroxisome Centriole 3  The Cytoskeleton ▪Microtubules, ▪Microfilaments, ▪Intermediate filaments Determine the shape of cell Contribute to movement of the cell Organize cellular contents 4 Fifth edition. | New York : W.W. Norton & Company,  Cytoplasmic Inclusions Temporary structures, nonliving accumulations, not essential to cell survival Stored cellular products Glycogen Fat droplets A portion of an absorptive cell showing Pigment granules, glycogen and lipid inclusions. Secretory granules 5  Nucleus Nuclear Envelope Chromatin Nucleolus Nuclear Matrix 6  CELL MEMBRANE = PLASMA MEMBRANE (Plasmalemma) ALL CELLS-BOTH PROKARYOTIC AND EUKARYOTIC-are surrounded by a plasma membrane, which defines the boundary of the cell and separates its internal contents from the environment. Only 7.5 nm thick. Invisible by light microscope. Visible only with Electron Microscope. 7  Cell membrane participates in numerous functions of the cell: Maintains essential differences between the cytosol and extracellular environment. Regulates the traffic of ions and macromolecules in and out of the cell. Possesses devices for attachment to other cells. Possesses specializations for cell-to-cell communication. Possesses antigenic macromolecules that are the basis for the cell recognition. Receptors for hormones and other environmental signals. Both isolates the cytoplasm and mediates interactions between the cell and its environment. 8  9 Fifth edition. | New York : W.W. Norton & Company,  CELL MEMBRANE Common general structure: Assemblies of lipid and protein molecules. Dynamic, fluid structures. Most of their molecules are able to move. Lipid molecules are arranged as a continuous double layer. Asymmetrical structures. Fluid Mosaic Model (Today accepted model) Singer&Nicholson 1971. Fluid mosaic model "Membrane proteins globular and float like icebergs in a sea of lipid." 10  Fluid Mosaic Model 11 Fifth edition. | New York : W.W. Norton & Company, Fluid Mosaic Model 12 13  Membrane Lipids Form Bilayers in Water Each lipid has a hydrophilic (“water-loving”) head and a hydrophobic (“water-fearing”) tail. The most abundant lipids in cell membranes are the phospholipids, which have a phosphate-containing, hydrophilic head linked to a pair of hydrophobic tails. 14 Fifth edition. | New York : W.W. Norton & Company,  Membrane Lipids Form Bilayers in Water Phosphatidylcholine has the small molecule choline attached to a phosphate group as its hydrophilic head. The “phosphatidyl” part of the name of a phospholipid refers to the phosphate – glycerol – fatty acid portion of the molecule. 15 Fifth edition. | New York : W.W. Norton & Company,  16 Fifth edition. | New York : W.W. Norton & Company,  Membrane Lipids Form Bilayers in Water Molecules with both hydrophilic and hydrophobic parts are termed amphipathic, a property shared by other types of membrane lipids, including the cholesterol, which is found in animal cell membranes and the glycolipids, which have sugars as part of their hydrophilic head. Having both hydrophilic and hydrophobic parts plays a crucial part in driving these lipid molecules to assemble into bilayers in an aqueous environment. 17  18 Fifth edition. | New York : W.W. Norton & Company, Pure phospholipids can form closed, spherical liposomes. (A) An electron micrograph of phospholipid vesicles (liposomes) showing the bilayer structure of the membrane. (B) A drawing of a small, spherical liposome seen in cross section. (A, courtesy of Jean Lepault.) 19  The Lipid Bilayer Is a Flexible Two-dimensional Fluid The aqueous environment inside and outside a cell prevents membrane lipids from escaping from the bilayer. The membrane therefore behaves as a two- dimensional fluid, a fact that is crucial for membrane function and integrity. The lipid bilayer is also flexible. it is able to bend. 20  1. Lateral diffusion: Structural Integrity (frequently) Lipids can move laterally. exchange places with their neighbors within a monolayer. (a single lipid molecule can diffuse the length of a bacterial cell (2 micron) in about one second) 2. Rotation: Lipids can rotate about their long axis. 3. Flip-flop : (rarely occurs by itself-once a month) (energetically unfavorable) migrate from one monolayer to the other. Phospholipid translocators catalyze the rapid flip-flop in ER membrane.) (Very important for lipid synthesis in the ER. 4. Flexion: The carbon chains (tails) are flexible. 21 Fifth edition. | New York : W.W. Norton & Company,  The hydrocarbon tail with no double bonds has a full complement of hydrogen atoms and is said to be saturated. The chain that harbors a double bond does not contain the maximum number of hydrogen atoms and is said to be unsaturated. Each double bond in an unsaturated tail creates a small kink in the tail which makes it more difficult for the tails to pack against one another. For this reason, lipid bilayers that contain a large proportion of unsaturated hydrocarbon tails are more fluid than those with lower proportions. 22 Fifth edition. | New York : W.W. Norton & Company, MEMBRANE LIPIDS I - Phospholipids II - Cholesterol III - Glycolipids 23  MEMBRANE LIPIDS 1 - Phospholipids: A mixture of phospholipids are organized in a bilayer. Phosphatidyl choline (neutral) Sphingomyelin (neutral) Phosphatidyl serine (-) Phosphatidyl etanolamine (neutral) Phosphatidyl inositol (-) (found in small amounts but plays important role in cell signalling) 24  Lipid Asymmetry 25 Fifth edition. | New York : W.W. Norton & Company, Lipid Asymmetry 26 The asymmetry of the lipid bilayer is functionally important 27 Fifth edition. | New York : W.W. Norton & Company, Fluidity of the membranes is dependent upon ; Lipid composition Cholesterol content Temperature 28  II - Cholesterol In animal cells, membrane fluidity is modulated by the inclusion of the cholesterol. Abundant in the plasma membrane of mammalian cells ᷉ (%20) Cholesterol molecules are short and rigid. They fill the spaces between neighboring phospholipid molecules left by the kinks in their unsaturated hydrocarbon tails. In this way, cholesterol tends to stiffen the bilayer, making it less flexible, as well as less permeable. 29  II - Cholesterol 30 Fifth edition. | New York : W.W. Norton & Company,  III - Glycolipids Glycolipids located mainly in the plasma membrane, and only in the noncytosolic half of the bilayer. Their sugar groups face the cell exterior. They form part of a continuous coat of carbohydrate that surrounds and protects animal cells. Glycolipid molecules acquire their sugar groups in the Golgi apparatus. There are no flippases that transfer glycolipids to the cytosolic side. When a glycolipid molecule is finally delivered to the plasma membrane, it displays its sugars to the exterior of the cell. 31 32  MEMBRANE PROTEINS The membrane proteins perform most of the membrane’s specific functions. Typical cell membrane: 50% protein by mass. 33 Fifth edition. | New York : W.W. Norton & Company,  Function of membrane proteins Transport molecules into and out of cells. (Transport proteins) Receive signals from hormones and other chemicals, Transmit those signals to the cell interior (receptors) Act as anchors for cytoskeletal components and receptors for extracellular matrix components (Integrin: fibronectin, laminin receptor) Various enzymes allow different chemical reactions (membrane-associated reactions) Serve as antigens 34  35 Fifth edition. | New York : W.W. Norton & Company,  MEMBRANE PROTEINS The outer and inner regions of the plasma membrane do not contain same types of proteins and equal amounts of proteins (membrane asymmetry) Transmembrane proteins are amphipathic. 36 Fifth edition. | New York : W.W. Norton & Company,  MEMBRANE PROTEINS Other membrane proteins are located almost entirely in the cytosol and are associated with the cytosolic half of the lipid bilayer by an amphipathic α helix exposed on the surface of the protein. 37 Fifth edition. | New York : W.W. Norton & Company, MEMBRANE PROTEINS Some proteins lie entirely outside the bilayer, on one side or the other, attached to the membrane only by one or more covalently attached lipid groups. 38 Fifth edition. | New York : W.W. Norton & Company, MEMBRANE PROTEINS Other proteins are bound indirectly to one or the other face of the membrane, held in place only by their interactions with other membrane proteins. 39 Fifth edition. | New York : W.W. Norton & Company,  MEMBRANE PROTEINS Proteins that are directly attached to the lipid bilayer— whether they are transmembrane, associated with the lipid monolayer, or lipid-linked—can be removed only by disrupting the bilayer with detergents, Such proteins are known as integral membrane proteins. The remaining membrane proteins are known as peripheral membrane proteins; they can be released from the membrane by more gentle extraction procedures that interfere with protein–protein interactions but leave the lipid bilayer intact. 40  MEMBRANE PROTEINS 1- Integral (intrinsic) proteins (Interact directly with the hydrophobic core, they penetrate the lipid bilayer) Some of the integral proteins that completely cross the membrane are called: TRANSMEMBRANE PROTEINS Single Pass Alpha Helix, polypeptide chain crosses lipid bilayer only once (i.e.GF receptors) Multiple Pass Alpha Helix, polypeptide chain crosses multiple times (i.e.G protein coupled receptors) Beta Sheet Barrel (found in the outer membrane of mitochondria, chloroplasts, and many bacteria, porin proteins) Some others are anchored to the cytosolic surface by an amphiphilic alpha helix 41  MEMBRANE PROTEINS Lipid Anchored Membrane Proteins Some membrane proteins are located in the cytosol and attached to the cytosolic monolayer by a fatty acid chain Other membrane proteins are exposed to external cell surface and attached to the lipid bilayer by an oligosaccharide that is bound to phosphotidyl inositol in the outer lipid layer (Glycosyl Phosphatidyl Inositol anchor (GPI anchor) 42  MEMBRANE PROTEINS Peripheral (extrinsic) proteins (Do not interact directly with the hydrophobic core, they are bound to the surface) Bind to the Integral proteins (by protein-protein interaction) 43 44 Frye and Edidin fused human and mouse cells in culture to produce human–mouse cell hybrids (Figure 15.5). They then analyzed the distribution of proteins in the membranes of these hybrid cells using antibodies that specifically recognize proteins of human and mouse origin. These antibodies were labeled with different fluorescent dyes, so the human and mouse proteins could be distinguished by fluorescence microscopy. Within 40 minutes after fusion, the mouse and human proteins became intermixed over the surface of hybrid cells, indicating that they moved freely through the plasma membrane. 45  MEMBRANE CARBOHYDRATES All eukaryotic cells have carbohydrate on their surface. They are located only on the noncytosolic (outer) surface. (Asymmetrical) Glycoproteins CELL COAT GLYCOCALIX Glycolipids Both glycoproteins and glycolipids are abundant in eukaryotic cell membranes. absent from the inner mitochondrial membrane and the chloroplast lamellae. 46  47 Fifth edition. | New York : W.W. Norton & Company,  Functions of membrane Carbohydrates 1- Important in cellular contacts and adhesion (Maintaining the integrity of the tissue) transient cell-cell adhesion processes, 2- Acts as a barrier to penetration of large particles. 3- Protect the plasma membrane against low pH, the effect of bile salts (intestinal epithelium) prevents damage to cell membranes by digestive enzymes. 4- Cell to cell recognition, cell to matrix recognition. 5- Some glycolipids also act as binding sites for substances taken up by cells. i.e. Peptide hormones and some molecules that act as cell poisons (cholera and tetanus toxins). 48 49  Functions of membrane Carbohydrates Several viruses and bacteria also use glycolipids and glycoproteins of animal plasma membrane as recognition and attachment sites. CD4 (T lymphocyte cell surface glycoprotein) act as binding site for HIV (AIDS) virus responsible for the various human blood types (A,B,O antigens) Cell surface carbohydrates markers of red blood cells responsible for the ABO blood groups. 50  Blood group antigens Arrangement of the sugar chains (genetically determined) of an individual with type A blood differ from those of an individual with type B blood. Carbohydrate portion constitute the antigenic determinant. 51  Blood group antigens If their membrane glycoproteins and glycolipids contain different carbohydrate markers: Transfused blood will be recognized as foreign will cause immune response If carbohydrate organization of DONOR'S CELLS and RECIPIENT'S CELLS are the same No immunological response 52  Blood group antigens A,B,O antigens are structurally related oligosaccharides linked to lipids or proteins. All people have the enzymes that synthesize the “ O “ antigen. O antigen is composed of, fucose, galactose, N- acetylglucosamin, glucose. A antigen is similar to “ O” except an N-acetylgalactosamin residue. B antigen is similar to “ O” except for an extra galactose residue attached to the outer galactose. 53  Blood group antigens Type “A” Blood have the enzyme that adds the Extra N-acetyl galactosamine Type “B” Blood have the enzyme that adds the Extra galactose Type “AB” blood synthesize “A” and “B” antigens Type “O” blood make only the “O” antigen 54 55 56