IB104 - Lecture 9 - Membranes

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1 There have been many magnificent boats built to try to reach 50 knots. This was the creation of an Australian team that held the record for more than a decade, from 1993 till 2005, at 46.5 knots with their solid wing sail rigged on three planning pods, called Yellow Pages Endeavour. IB104 - Lecture 9 - Membranes Reading - Chapter 5 Introduction 1. A membrane surrounds the entire cell - the cell or plasma membrane. 2. Membranes also surround the nucleus, mitochondria, cytomembrane system, lysosomes, and all other intra-cellular organelles. 3. Thus membranes determine how cells interact with their environment, including other cells. 4. They also determine how organelles interact with the cytoplasm. 5. Their basic structure is a phospholipid bilayer with embedded s. 6. The phospholipid bilayer provides the basic properties of selective permeability. 7. The embedded and associated s provide additional functions ranging from movement of ions across the membrane to perception of light and chemicals to endocytosis of large molecules. The phospolipid bilayer 1. Plasma/cell and organelle membranes are all phospholipid bilayers. A phospholipid is a triglyceride with one of the fatty acids replaced with a complicated phosphate group. 2. Phospholipids therefore spontaneously form spheres of phospholipid bilayers in water. The hydrophobic lipid tails interact with each other, excluding water. The hydrophilic phosphate heads interact with water on either side. Fatty acids are hydrophobic, while the phosphate group is hydrophilic. Thus phospholipids are amphipathic, wanting to interact both with water and each other. Cholesterol (sterol) H 2 O H 2 O Cholesterol has similar amphipathic characteristics, and hence generally resides within membranes. Phosphatidylcholine (phospholipid) 1

2 3. Phospholipid bilayers are selectively permeable. They are permeable to small non-polar molecules, most famously oxygen and carbon dioxide, as well as lipid-soluble molecules. They are impermeable to large, or polar, or charged molecules, e.g. ions. oxygen, carbon dioxide, glucose and other large, polar, and other small, nonpolar water-soluable molecules; ions molecules! (e.g., H+, Na+, K+, CA++, CI ); water molecules! 5. Osmosis is the process whereby water moves across a membrane to equalize the concentrations of ions and other solutes on either side of the membrane. For example, cells will swell in distilled water, and shrink in salt water. 2% sucrose Drink companies like Gatorade sell isotonic drinks. distilled water 10% sucrose 2% sucrose Hypotonic Hypertonic Isotonic 4. Diffusion of water across cell membranes is strange. A pure phospholipid bilayer is impermeable to water, however water readily moves across real cell membrane. Instead water crosses through specialized water channel s called aquaporins. Klaus Schulten in Biophysics generated the image on the left below, showing blue water molecules crossing the membrane (pink region) through such a water channel made up of multiple aquaporins (a single one is on the right). Dealing with the differences between salty and fresh water has serious consequences for many fish that move been these two kinds of habitats. Most famously, salmon smolts leaving their river birthplaces spend weeks adjusting to the ocean, while returning adults must spend several days in the brackish water at river mouths adjusting their physiology. 2

3 The embedded s 1. Each has at least one stretch of ~20 hydrophobic amino acids that form an alpha helix to cross the phospholipid bilayer and embed in the membrane. They can move fairly freely around within the membrane. adhesion passive transporter recognition receptor 2. In addition to the aquaporins or water channels, there are many other channel s that facilitate movement of impermeable molecules across membranes. Your textbook calls this passive transport. The best known are the various specific ion channels, e.g. for sodium, potassium, and calcium ions in nerve cells (Na +, K +, Ca ++ ). high lipid bilayer Concentration gradient ATP cytoskeletal s active transporter (calcium pump) active transporter (ATPase pump) cytoplasm low Diffusion of lipid-soluble substances Passive transport of water-soluble substances Active transport through ATPase The opening and closing of these channels is regulated so that ions can only diffuse down their concentration gradient when the relevant channel is open - this is facilitated diffusion or passive transport. For example, in nerve cells, an electric signal is transmitted by first opening sodium channels to allow sodium ions to diffuse into the cell down their established concentration gradient, followed by opening of potassium channels allowing potassium ions to diffuse out of the cell shortly thereafter. 3. Sometimes ions must be moved against their concentration gradient, in which case this is active transport. This requires energy in the form of ATP. In nerve cells there is a spectacular called the sodium/potassium pump, which couples active transport of a sodium ion out of the cell with transport of a potassium ion into the cell, both against their concentrations gradients, but without creating an electrical gradient. Donation of a phosphate from ATP to the drives the first step; removal of the phosphate from the drives the second step. 3

4 4. Cystic fibrosis is a unusually common genetic disease involving failure of chlorine ion transport across membranes. The cause is a mutation in a type of transporter known as CFTR, for cystic fibrosis transporter/receptor. While there are many possible mutations that can inactivate CFTR, a particular mutant, in which one amino acid of the ~1500 aas in the is missing, is particularly common in Caucasians. Failure of chlorine transport causes a variety of problems, but most importantly build up of mucous in the lungs, which allows infection with bacteria, especially Pseudomonas aeruginosa, which can eventually kill. Read the intro to chapter 5 for more. 5. All large molecules must be actively transported across membranes, e.g. the glucose transporter. A change in the shape or conformation of the moves a glucose molecule across the membrane. There are hundreds of different transporters for different molecules. solute (glucose)! low high! glucose transporter! 6. Receptors interact with molecules outside cells and send signals inside cells. The internal signal is commonly cyclic AMP. For example, opsins are receptors that can perceive light. These s have seven transmembrane domains. Many similar s recognize all sorts of hormones, and I work on the chemoreceptors of insects and nematodes, which like us have hundreds to thousands of different chemoreceptors to detect all the chemicals they and we smell and taste. 7. Cell adhesion s interact with surfaces or with s on other cells, indeed commonly these are homophilic interactions, meaning that the extracellular part of an adhesion interacts within other copies of itself on neighboring cells, thereby holding them all together in a tissue. The intracellular part of these s generally binds to components of the cytoskeleton, making the adhesion strong. This diagram shows one example, a cadherin, but there are many of these adhesion s. 4

5 8. Recognition s provide a means for differentiating self from non-self. As you will see later, this is particularly important for the immune system and generally prevents our adaptive immune system from attacking our own cells and tissues. Many terrible diseases involve failure of this step, e.g. juvenile diabetes and arthritis. 9. Viruses commonly take advantage of the embedded s in cell membranes to attach to and enter cells. These s are sometimes called viral receptors, but this is inappropriate as they all have useful functions in cells, the viruses are just exploiting them. E.g. HIV attaches to two s on specific white blood cells. The few people who are resistant to HIV infection and hence AIDS are mutant for one or other of these two receptors (neither of which is essential to live). Outside These recognition s must be highly variable and there are many of them, making the repertoire of any individual different from any other individual. The major ones are called HLAs, e.g. above, and can bind foreign peptides (yellow) and present them to the immune system (TCR). Cell membrane Inside 10. Endocytosis is a receptor-mediated method for bringing large molecules into cells. Pits lined with receptors endocytotic linked to a called clathrin form on cell membranes, and eventually invaginate and pinch off, bringing the bound molecules into s inside the cell. These s can interact with lysosomes and other intra-cellular s like the Golgi body. clathrin Golgi body exocytotic 11. Phagocytosis is the process whereby cells envelop and ingest other cells, for example, amoebae or white blood cells eating bacteria. Once engulfed and surrounded by a part of the cell membrane that buds off as a inside the cell, the bacteria are digested by enzymes in a lysosome with which the has fused. edible bacterium amoeba phagocytic lysosome 5

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