Membrane_transport_23.pptx

Plasma membrane • Learning objectives • Plasma membrane: structure and function • Lipid component of plasma membrane and their function • Membrane proteins • Diagram of plasma membrane Case Study 1: • Presentation: 56 year old man presenting with lethargy, polyuria, polydipsia, polyphagia, and w...

Plasma membrane • Learning objectives • Plasma membrane: structure and function • Lipid component of plasma membrane and their function • Membrane proteins • Diagram of plasma membrane Case Study 1: • Presentation: 56 year old man presenting with lethargy, polyuria, polydipsia, polyphagia, and weight loss. • Physical exam: Overweight, BMI of 29, otherwise WNL • Blood work: glucose: 232 (reference: 70-100mg/dL) • Urinalysis: 3+ glucose Membrane-bound organelles Rough endoplasmic reticulum Smooth endoplasmic Golgi reticulum apparatus Lysosom e Peroxisom e Nucleu s Nuclear envelope Nucleoplas m Nucleolus Mitochondrio n Nonmembranebound Ribosomes organelles Free ribosome s Bound ribosome s Cytoplas m Plasma membrane Centrosom e Proteasome s Modifications of plasma Microvill membrane i Cytoskeleto n Cili a Flagellu m Cytosol (intracellular fluid) Interstitial fluid Inclusion s Vesicle Cells perform general functions: Maintain integrity and shape of a cell Dependent on plasma membrane and internal contents Obtain nutrients and form chemical building blocks Harvest energy for survival Dispose of wastes Avoid accumulation that could disrupt cellular activities Some are also capable of cell division Make more cells of same type Help maintain tissue by providing cells for new growth and replacing dead cells The Plasma Membrane • Fluid mosaic model • Describes the organization of cell membranes • Hydrophobic interactions that cause bilayer • Phospholipids NOT bonded to each other • Weaker than covalent bonds • Phospholipids drift and move like a fluid • The bilayer is a mosaic mixture of phospholipids, steroids, proteins, and other molecules • Only small and nonpolar substances can easily penetrate through the plasma membrane without barrier Fluid Mosaic Model of The Plasma Membrane Membrane Lipids • 98% of molecules • Phospholipids • 75% of membrane lipids • Amphiphilic molecules arranged in a bilayer • Hydrophilic heads (polar) • Hydrophobic tails (nonpolar) • Drift laterally and rotate 4.2a Lipid Components 2 • Phospholipids • “Balloon with two tails” • Polar and hydrophilic “head”; two nonpolar and hydrophobic “tails” • Form two parallel sheets of molecules lying tail to tail • Hydrophobic tails form internal environment of membrane • Hydrophilic polar heads directed outward • Phospholipid bilayer is the basic structure of the framework • Ensures cytosol remains inside the cell • Ensures interstitial fluid remains outside 11 4.2a Lipid Components 3 • Cholesterol • Four-ring lipid molecule scattered within phospholipid bilayer • Strengthens membrane • Stabilizes membrane against temperature extremes • Glycolipids • Lipids with attached carbohydrate groups • Located on outer phospholipid region only • Helps form glycocalyx 12 Membrane Lipids • Cholesterol • 20% of the membrane lipids • Holds phospholipids still and can stiffen membrane • Glycolipids • 5% of the membrane lipids • Phospholipids with short carbohydrate chains on extracellular face • These carbohydrate extend like sugar antennae • Contributes to glycocalyx Cholesterol • 4 ring lipid molecule • Scattered within the inner hydrophobic region of the phospholipid bilayer • Strengthens the membrane • Stabilizes if temp increases The Glycocalyx • Unique fuzzy coat external to the plasma membrane • Carbohydrate moieties of membrane glycoproteins and glycolipids • Unique in everyone but identical twins • Functions • Protection • Cell adhesion • Immunity to infection • Fertilization • Defense against cancer • Embryonic development • Transplant compatibility http://www.columbia.edu/itc/hs/medical/sbpm_histology_old/lab/ lab01_micrograph.html Membrane Proteins • 2% of the molecules in plasma membrane • 50% of its weight • Transmembrane proteins • Peripheral proteins 4.2b Membrane Proteins 1 • Membrane proteins • Half of plasma membrane by weight • Float and move in fluid bilayer • Performs most of membrane’s functions • Two structural types • Integral • Peripheral 17 4.2b Membrane Proteins 2 Integral proteins • Embedded within, and extend across, phospholipid bilayer • Hydrophobic regions interact with hydrophobic interior • Hydrophilic regions are exposed to aqueous environments on either side of membrane • Many are glycoproteins with attached carbohydrate groups Peripheral proteins • Not embedded in lipid bilayer • Loosely attached to external or interior surfaces of membrane 18 4.2b Membrane Proteins 3 • Proteins are also categorized functionally: • Transport proteins • Regulate movement of substances across membrane • For example, channels, carrier proteins, pumps, symporters, and antiporters • Cell surface receptors • Bind molecules called ligands • For example, neurotransmitters released from a nerve cell that binds to a muscle cell to initiate contraction • Identity markers • Communicate to other cells that they belong to the body • These markers are used to distinguish healthy cells from cells to be destroyed 19 4.2b Membrane Proteins 4 • Functional categories of proteins (continued ) • Enzymes • May be attached to either internal or external surface of a cell • Catalyze chemical reactions • Anchoring sites • Secure cytoskeleton to plasma membrane • Cell-adhesion proteins • Perform cell-to-cell attachments 20 Membrane Proteins Functions of membrane proteins Second Messenger System Microvilli • Extensions of membrane (1–2  m) • Increase cell’s surface area • “Brush Border” • Milking action • Actin filaments shorten • Push contents into cell • “Surface area volume ratio” Cilia • Hairlike processes- 7– 10  m long • Single, nonmotile primary cilium • “Antenna” • Sensory in inner ear, retina, nasal cavity, and kidney • Motile cilia • Respiratory tract, uterine tubes, ventricles of the brain, efferent ductules of testes • Sweep substances across surface in same direction • Power strokes followed by recovery strokes Cilia • Axoneme—core of cilia that is the structural basis for movement • 9 + 2 array of microtubules • Nine pairs form basal body • Anchors cilium • Dynein arms “crawl” up adjacent microtubule, bending the cilia • Uses energy from ATP • Saline layer • Chloride pumps pump Cl- into ECF • Na+ and H2O follows • Cilia beat freely in saline layer Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Cystic Fibrosis • Saline layer at cell surface due to chloride pumps move Cl- out of cell. Na+ ions and H2O follow • Cystic fibrosis—hereditary disease causing abnormal chloride pumps • Chloride pumps fail to create adequate saline layer on cell surface • Thick mucus plugs pancreatic ducts, respiratory tract, and genital tracts • Inadequate digestion of nutrients, absorption of oxygen, and transport of gametes • Chronic respiratory infections • Life expectancy of 35-37 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Mucus Saline layer Epithelial cells • Cystic fibrosis is an Inherited disease caused by mutations in a gene called the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The CFTR gene provides instructions for the CFTR protein. The CFTR protein is located in every organ of the body that makes mucus, including the lungs, liver, pancreas, and intestines, as well as sweat glands. The CFTR protein has also been found in other cells in the body, such as cells of the heart and the immune system. The mutations in the CFTR gene cause the CFTR protein to not work properly. This causes thick, sticky mucus and blockages in the lungs and digestive system. Flagella • Tail of sperm • Whiplike structure with axoneme identical to cilium • Much longer • Movement is more undulating, snakelike • No power stroke or recovery stroke as in cilia Membrane Permeability • Selective permeability • The ability of a cell membrane to control which substances and how much of them enter or leave the cell • Allows the cell to maintain a difference between its internal environment and extracellular fluid • Supplies the cell with nutrients, removes wastes, and maintains volume and pH What types of substances can cross the plasma membrane? How do substances cross the plasma membrane? 1. Diffusion 2. Osmosis 3. Filtration 4. Facilitated diffusion 5. Active transport 6. Vesicular transport: Endocytosis and exocytosis Membrane Transport • Passive transport mechanisms = no energy input required • HIGH  LOW concentration • random molecular motion of particles provides the necessary energy • filtration, diffusion, osmosis, facilitated diffusion • Active transport mechanisms = require energy input • Active transport and vesicular transport • LOW  HIGH concentration 4.3 Membrane Transport 1 • Plasma membrane • Serves as physical barrier between cell and fluid that surround it (interstitial fluid) • Regulates movement into and out of a cell • Establishes and maintains electrochemical gradient • Functions in cell communication Membrane transport • Process of obtaining and eliminating substance across the plasma membrane • Two categories • Passive processes • Active processes 35 Membrane Transport • Figure 4.7 • Access the text alternative for slide images. 36 4.3 Membrane Transport 2 • Substances moved across a membrane • Passive processes of membrane transport • Do not require energy • Depend on substances moving down concentration gradient • Move from area of more substance to area of less • Two types: diffusion, osmosis • Active processes of membrane transport • Require energy • Substance must be moved up its concentration gradient (active transport) • Membrane-bound vesicle must be released (vesicular transport) 37 4.3a Passive Processes: Diffusion 1 • Diffusion • Net movement of ions or molecules from area of greater concentration to area of lesser concentration • Down the concentration gradient • Due to kinetic energy (energy of motion) of ions/molecules • Influenced by temperature • Increased temp, increased kinetic energy and rate of diffusion 38 4.3a Passive Processes: Diffusion 2 • Diffusion (continued) • Also influenced by “steepness” of concentration gradient • Measure of the difference in concentration between two areas • Steeper gradient causes faster rate of diffusion • If unopposed, diffusion continues until substance reaches equilibrium • Molecules evenly distributed throughout a given area 39 Diffusion 4.3a Passive Processes: Diffusion 3 • Simple diffusion • Molecules move unassisted between phospholipid molecules • Small and nonpolar solutes • Include: respiratory gases (O2 and CO2), some fatty acids, ethanol, urea • Not regulated by plasma membrane • Movement dependent on concentration gradient • Continues to move as long as gradient exists 41 Simple Diffusion of Solutes • Figure 4.9 • Access the text alternative for slide images. 42 4.3a Passive Processes: Diffusion 4 • Facilitated diffusion • Transport process for small charged or polar solutes requires assistance from plasma membrane proteins • Two types: • Channel-mediated diffusion • Carrier-mediated diffusion 43 4.3a Passive Processes: Diffusion 5 • Channel-mediated diffusion • Movement of small ions through water-filled protein channels • Channels specific for one ion type • Leak channels • Continuously open • Gated channel • Usually closed • Opens in response to stimulus for fraction of second • Important in normal function of muscle and nerve cells 44 Channel-Mediated Diffusion • Figure 4.10a • Access the text alternative for slide images. 45 4.3a Passive Processes: Diffusion 6 • Carrier-mediated diffusion • Small polar molecules assisted across membrane by carrier protein • Binding of substance causing change in carrier protein shape • Releases substances on other side of membrane • Moves substances down their gradient • Uniporter—carrier transporting only one substance • The number of channels and carriers determines the max rate of substance transport 46 The Rate of Diffusion • • • • • • • • Size/Molecular weight Temperature Steepness of the concentration gradient Charge Hydrostatic Pressure Permeability of membrane Surface area of membrane Thickness of the membrane Osmosis • Osmosis—diffusion of water from one side of a selectively permeable membrane to the other • From side with higher water concentration to side with lower water concentration • Reversible attraction of water to solute particles forms spheres of hydration • Makes those water molecules less available to diffuse back to the side from which they came Osmosis • Movement of water by osmosis • Dependent upon concentration gradient between cytosol and solution surrounding cell • Water moves down gradient until equilibrium is reached • For example, moves from solution of 1% solutes (99% water) into solution containing 3% solutes (97% water) Osmosis • Aquaporins—channel proteins in plasma membrane specialized for passage of water • Increase rate of osmosis by installing aquaporins • Decrease rate by removing them • Significant amounts of water diffuse even through the hydrophobic, phospholipid regions of the plasma membrane Osmosis • Osmotic pressure—amount of hydrostatic pressure required to stop osmosis • Tonicity • The relative concentrations of solutes in two fluids separated by a selectively permeable membrane • Terms that describe relative concentration of solutions: • Isotonic • Hypotonic • Hypertonic 4.3b Passive Processes: Osmosis 6 • Isotonic solution • Both cytosol and solution have same relative concentration of solutes • For example, normal saline with a concentration of 0.9% NaCl • Commonly used in IV solutions • No net movement of water 53 4.3b Passive Processes: Osmosis 7 • Hypotonic solution • Solution has a lower concentration of solutes, higher concentration of water than in cytosol • For example, erythrocytes in pure water • Water moves down concentration gradient from outside cell to inside • Increases volume and pressure of cell • Lysis—rupturing of red blood cells occurs if difference is large enough • Hemolysis—rupturing erythrocytes 54 4.3b Passive Processes: Osmosis 8 • Hypertonic solution • Solution with a higher concentration of solutes than cytosol • For example, erythrocytes in 3% NaCl water solution • Water moves down concentration gradient • Moves from inside cell to outside • Decreases volume and pressure of cell • Crenation—cell shrinks 55 How can tonicity change a cell? Filtration • Filtration - particles are driven through a selectively permeable membrane by hydrostatic pressure Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Solute Blood pressure in capillary forces water and small solutes such as salts through narrow clefts between capillary cells. Water Capillary wall Red blood cell • Examples • filtration of nutrients through gaps in blood capillary walls into tissue fluids • filtration of wastes from the blood in the kidneys while holding back blood cells and proteins Clefts hold back larger particles such as red blood cells. Membrane Carriers ******* • Transmembrane proteins • Either Active transport or facilitated diffusion • Uniport • carries 1 solute at a time • Symport (cotransport) • carries 2+ solutes simultaneously in same direction • Antiport (countertransport) • carries 2+ solutes in opposite directions Protein-Mediated Transport • Facilitated diffusion—carrier-mediated transport of solute through a membrane down its concentration gradient • Does not need ATP Protein-Mediated Transport • Active transport—carrier-mediated transport of solute through a membrane up (against) its concentration gradient • ATP energy used Active Transport • Leakage channels located in membranes result in leaking of Na+ into the cell and leaking of K+ out of cell • Both travel down their concentration gradients • Na+-K+ pump works as an antiporter that pumps Na+ out of cell and K+ back into cell against their concentration gradients • Maintains electrochemical gradients, which involve both concentration and electrical charge of ions • Essential for functions of muscle and nerve tissues 4.4 Resting Membrane Potential • Plasma membrane establishes and maintains electrochemical gradient—resting membrane potential (RMP) • Essential for muscle and nerve cell function 62 4.4a Introduction • Electrical charge difference at plasma membrane • Membrane potential—potential energy of charge difference • Resting membrane potential (RMP)—potential when a cell is at rest • Two conditions for RMP: 1. Unequal distribution of ions/molecules across plasma membrane • More K+ in cytoplasm than in interstitial fluid • More Na+in interstitial fluid than in cytoplasm • Due to Na+/K+ pumps 2. Unequal relative amounts of positive and negative charges • More positive on outside than inside of cell 63 • Sodium-potassium pump • Most studied pump • Basically is an enzyme, called Na+-K+ ATPase, that pumps Na+ out of cell and K+ back into cell • Located in all plasma membranes, but especially active in excitable cells (nerves and muscles) Resting Membrane Potential (RMP) • Figure 4.20 • Access the text alternative for slide images. 65 4.4b Establishing and Maintaining RMP 1 • Most important ions = Na+ and K+ • Movement depends on electrochemical gradient • The role of K+ • Most important determinant in specific value of RMP • K+ moves down steep concentration gradient through leak channels from cytosol to interstitial fluid • Negatively charged proteins remain inside cell • Electrochemical gradient • Positive charge outside repels movement of K+ out • Negative charge on inside attracts K+ inward • K+ moves until equilibrium is reached 66 4.4b Establishing and Maintaining RMP 2 • The role of Na+ • Na+ diffuses into cells from interstitial fluid to cytosol simultaneous to the loss of K+ • Enters through Na+ leak channels • Down concentration gradient • Pulled by electrical gradient • Leak channels prevent as much Na into the neuron a K+ out • Inside becomes more positive 67 4.4b Establishing and Maintaining RMP 3 • Maintaining an RMP • Na/K pumps significant • • • • • Maintains K+ and Na+ gradients following their diffusion Na+ pumped out K+ pumped in Opposite directions Against concentration gradient 68 Section 4.4 What did you learn? 14. Define a resting membrane potential. 15. Explain how the resting membrane potential is established and maintained including the role of K+, Na+, and Na+/K+ pumps. 69 4.5 Cell Communication • Plasma membrane serves an important role in cell communication • Structures such as glycolipids and glycoproteins facilitate both direct interaction between cells as well as recognition and response to external molecular signals 70 Sodium-Potassium ATPase Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. • Each pump cycle consumes one ATP and exchanges three Na+ for two K+ • Keeps the K+ concentration higher and the Na+ concentration lower within the cell than in ECF • Necessary because Na+ and K+ constantly leak through membrane • Half of daily calories utilized for Na+−K+ pump • Cell swelling stimulates the Na+−K+ pump to ion concentration, osmolarity and cell swelling Sodium-Potassium ATPase • Maintenance of a membrane potential in all cells • Pump keeps inside more negative, outside more positive • Necessary for nerve and muscle function • Heat production • Thyroid hormone increases number of Na + −K+ pumps • Consume ATP and produce heat as a byproduct Vesicular Transport • Endocytosis • The formation of a vesicle from cell membrane, enclosing materials near the cell surface and bringing them into the cell • Exocytosis • The fusion of a vesicle with the cell membrane, secreting its contents to the ECF • Replacement of plasma membrane removed by endocytosis Three Pathways of Endocytosis • Phagocytosis • Larger target particles such as microbes or cellular debris are engulfed by pseudopods which merge as a vesicle • Pinocytosis • A less selective endocytic pathway that brings solutes in bulk into the cell plasma membrane vacuole a. Phagocytosis solute vesicle b. Pinocytosis • Receptor-mediated endocytosis • Specific molecules bind to surface receptors, which are then enclosed in an endocytic vesicle receptor protein solute coated pit coated vesicle c. Receptor-mediated endocytosis plasma membrane aggregates of lipoproteins Membrane Cycling • Exocytosis and endocytosis continually replace and withdraw patches of the plasma membrane • New plasma membrane is created when membrane proteins and lipids are made in the ER, modified by Golgi bodies, and form vesicles that fuse with plasma membrane 4.5a Direct Contact Between Cells • Direct contact between cells is important for some cells to function • Examples: • Cells of immune system • Distinguishes normal cells from unhealthy cells • Sperm and oocyte • Egg with unique glycocalyx • Allows for recognition by sperm during fertilization • Cellular regrowth following injury • Damaged tissue replaced by cell division in epidermis • Cellular contact prevents overgrowth 79 Case Study 1: • Presentation: 56 year old man presenting with lethargy, polyuria, polydipsia, polyphagia, and weight loss. • Physical exam: Overweight, BMI of 29, otherwise WNL • Blood work: glucose: 232 (reference: 70-100mg/dL) • Urinalysis: 3+ glucose Diagnosis? • The ___________which both integrates the input information from the receptor and initiates output to the _____________ • Control center; effector