Chapter 7 Membrane Structure and Function, by Hugh Davson and James Danielli A sandwich model In 1972, J. Singer and G. Nicolson the placement of membrane proteins

Fig. 7-2 Hydrophilic head WATER Hydrophobic tail WATER Amphipathic molecules

Fig. 7-3 Phospholipid bilayer Hydrophobic regions of protein Hydrophilic regions of protein

Fig. 7-4 TECHNIQUE Extracellular layer Knife Proteins Inside of extracellular layer RESULTS Inside of cytoplasmic layer Cytoplasmic layer Plasma membrane Freeze fracture

Fig. 7-5 Lateral movement (~10 7 times per second) Flip-flop (~ once per month) (a) Movement of phospholipids (b) Membrane fluidity Fluid Viscous Unsaturated hydrocarbon tails with kinks Saturated hydro- carbon tails (c) Cholesterol within the animal cell membrane Cholesterol The fluidity of membrane

The steroid cholesterol has different effects on membrane fluidity at different temperatures At warm temperatures (such as 37°C), cholesterol restrains movement of phospholipids At cool temperatures, it maintains fluidity by preventing tight packing Cholesterol

Phytosterol The FDA has approved the following claim for phytosterols: "Foods containing at least 0.4 gram per serving of plant sterols, eaten twice a day with meals for a daily total intake of at least 0.8 gram, as part of a diet low in saturated fat and cholesterol, may reduce the risk of heart disease."* The mechanism behind phytosterols and the lowering of cholesterol occurs as follows: the incorporation of cholesterol into micelles in the gastrointestinal tract is inhibited, decreasing the overall amount of cholesterol absorbed (see cholesterol absorption inhibitor). This may in turn help to control body total cholesterol levels, as well as modify HDL, LDL and TAG levels. Many margarines, butters, breakfast cereals and spreads are now enriched with phytosterols and marketed towards people wishing to lower their cholesterol levels.micellesgastrointestinal tract cholesterol absorption inhibitormargarinesbuttersbreakfast cereals dietary sterols might increase the risk of aortic valve stenosis.[9]aortic valve stenosis[9]

Fig. 7-6 RESULTS Membrane proteins Mouse cell Human cell Hybrid cell Mixed proteins after 1 hour

Fig. 7-7 Fibers of extracellular matrix (ECM) Glyco- protein Microfilaments of cytoskeleton Cholesterol Peripheral proteins Integral protein CYTOPLASMIC SIDE OF MEMBRANE Glycolipid EXTRACELLULAR SIDE OF MEMBRANE Carbohydrate

Fig. 7-8 N-terminus C-terminus  Helix CYTOPLASMIC SIDE EXTRACELLULAR SIDE

Fig. 7-9 (a) Transport ATP (b) Enzymatic activity Enzymes (c) Signal transduction Signal transduction Signaling molecule Receptor (d) Cell-cell recognition Glyco- protein (e) Intercellular joining (f) Attachment to the cytoskeleton and extracellular matrix (ECM) Six major functions of membrane proteins:

Fig ER 1 Transmembrane glycoproteins Secretory protein Glycolipid 2 Golgi apparatus Vesicle 3 4 Secreted protein Transmembrane glycoprotein Plasma membrane: Cytoplasmic face Extracellular face Membrane glycolipid Synthesis and sideness of membranes

Concept 7.2: Membrane structure results in selective permeability

Fig Molecules of dye Membrane (cross section) WATER Net diffusion Equilibrium (a) Diffusion of one solute Net diffusion Equilibrium (b) Diffusion of two solutes

Lower concentration of solute (sugar) Fig H2OH2O Higher concentration of sugar Selectively permeable membrane Same concentration of sugar Osmosis Osmosis is the diffusion of water across a selectively permeable membrane

Hypotonic solution (a ) Animal cell (b ) Plant cell H2OH2O Lysed H2OH2O Turgid (normal) H2OH2O H2OH2O H2OH2O H2OH2O Normal Isotonic solution Flaccid H2OH2O H2OH2O Shriveled Plasmolyzed Hypertonic solution Fig Tonicity is the ability of a solution to cause a cell to gain or lose water

Aquaporin Aquaporins are integral membrane proteins Aquaporins are "the plumbing system for cells Agre said he discovered aquaporins "by serendipity." His lab had an N.I.H. grant to study the Rh blood group antigen. They isolated the Rh molecule but a second molecule, 28 kilodaltons in size (and therefore called 28K) kept appearing.

Fig EXTRACELLULAR FLUID Channel protein (a) A channel protein Solute CYTOPLASM Solute Carrier protein (b) A carrier protein (Shape change)

cystinuria 胱胺酸尿症 (#) caused by malfunctions in specific transport systems Cystinuria is characterized by the inadequate reabsorption of cystine during the filtering process in the kidneys, thus resulting in an excessive concentration of this amino acid.amino acid Cystine may precipitate out of the urine, if the urine is neutral or acidic, and form crystals or stones in the kidneys, ureters, or bladder.precipitateurineneutral or acidiccrystals Cystine?

2 Fig Active transport EXTRACELLULAR FLUID [Na + ] high [K + ] low [Na + ] low [K + ] high Na + CYTOPLASM ATP ADP P Na + P 3 K+K+ K+K+ 6 K+K+ K+K+ 5 4 K+K+ K+K+ P P 1 (Phosphorylation) (dephosphorylation)

Fig Passive transport Diffusion Facilitated diffusion Active transport ATP

How Ion Pumps Maintain Membrane Potential Membrane potential is the voltage difference across a membrane Voltage is created by differences in the distribution of positive and negative ions

collectively called the electrochemical gradient, drive the diffusion of ions across a membrane: –A chemical force (the ion ’ s concentration gradient) –An electrical force (the effect of the membrane potential on the ion ’ s movement) Two combined forces

An electrogenic pump is a transport protein that generates voltage across a membrane sodium-potassium pump : The sodium-potassium pump is the major electrogenic pump of animal cells proton pump The main electrogenic pump of plants, fungi, and bacteria is a proton pump

Fig EXTRACELLULAR FLUID H+H+ H+H+ H+H+ H+H+ Proton pump H+H+ H+H+ + + H+H+ – – – – ATP CYTOPLASM –

Cotransport: Coupled Transport by a Membrane Protein Cotransport occurs when active transport of a solute indirectly drives transport of another solute Plants commonly use the gradient of hydrogen ions generated by proton pumps to drive active transport of nutrients into the cell

Fig Proton pump – – – – – – ATP H+H+ H+H+ H+H+ H+H+ H+H+ H+H+ H+H+ H+H+ Diffusion of H + Sucrose-H + cotransporter Sucrose

Concept 7.5: Bulk transport across the plasma membrane occurs by exocytosis and endocytosis In exocytosis, transport vesicles migrate to the membrane, fuse with it, and release their contents –Many secretory cells use exocytosis to export their products In endocytosis, the cell takes in macromolecules by forming vesicles from the plasma membrane –There are three types of endocytosis: –Phagocytosis ( “ cellular eating ” ) –Pinocytosis ( “ cellular drinking ” ) –Receptor-mediated endocytosis

Fig PHAGOCYTOSIS EXTRACELL ULAR FLUID CYTOPLASM Pseudopodium “Food”or other particle Food vacuole PINOCYTOSIS 1 µm Pseudopodium of amoeba Bacterium Food vacuole An amoeba engulfing a bacterium via phagocytosis (TEM) Plasma membrane Vesicle 0.5 µm Pinocytosis vesicles forming (arrows) in a cell lining a small blood vessel (TEM) RECEPTOR-MEDIATED ENDOCYTOSIS Receptor Coat protein Coat ed vesi cle Coated pit Ligand Coat protein Plasma membrane A coated pit and a coated vesicle formed During receptor-mediated endocytosis (TEMs) 0.25 µm

You should now be able to: 1.Define the following terms: amphipathic molecules, aquaporins. 2.Explain how membrane fluidity is influenced by temperature and membrane composition 3.Distinguish between the following pairs or sets of terms: peripheral and integral membrane proteins; channel and carrier proteins; osmosis, facilitated diffusion, and active transport; hypertonic, hypotonic, and isotonic solutions

4.Explain how transport proteins facilitate diffusion 5.Explain how an electrogenic pump creates voltage across a membrane, and name two electrogenic pumps 6.Explain how large molecules are transported across a cell membrane