Membrane biochemistry. Red blood cell ghost Only plasmalemma Size known (7 µm) Gorter & Grendel 1925 Tension on surface Enough lipid for 2 layers

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2 Membrane biochemistry Red blood cell ghost Only plasmalemma Size known (7 µm) Gorter & Grendel 1925 Tension on surface Enough lipid for 2 layers

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4 Fig. 6.5

5 Osmosis water moves passively from high WATER concentration (for instance pure water) to low WATER concentration (where organic chemicals are dissolved) through a semipermeable membrane (passes water but not the organic molecules).

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7 Fig. 6.14

8 Membrane structure bilayer of lipids with protein in it lipid molecules drawn in this "cartoon" ball with two sticks. phospholipids with: (1) a polar (hydrophilic) head group (2) two hydrophobic fatty acid (acyl) tails

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10 rhodopsin 7 hydrophobic alpha helices of the protein fit into the hydrophobic part of the membrane (the milieu created by the fatty acid tails). retinal is the chromophore, the component (chromophore) that makes the protein [proteins are otherwise not colored] into a pigment. Retinal is a derivative of vitamin A. Rhodopsin is in the membranes of rods and cones, visual receptor cells

11 more Rhodopsin is the prototypical G proteincoupled receptor (GPCR), and GPCRs are used for hormones, neurotransmitterss, olfaction, taste and others.

12 Fig. 3.2

13 Membrane EM Robertson bilayer 2 "electron dense" lines stained osmium, electron dense heavy metal. Davson and Danielli membrane model. Fluid mosaic Singer and Nicolson freeze fracture replica apparatus. membranes break between the fatty acids from an angle with a platinum gun (shadow) from above with a carbon gun (to hold replica together), then the tissue is dissolved away.

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16 Membrane biochemistry (1) Phospholipids like phosphatidylcholine (lecithin) radioactively labeled phosphate separated on a TLC (thin layer chromatography) plate. (2) Cholesterol (3) Glycolipids Tay-Sachs, a hereditary lysosomal storage disease,1/30 American Jews carry, recessive, fatal at 6 mo - 5 yr

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18 Membrane physiology membrane have extremely high resistance. because the hydrophobic milieu in the center does not allow water, a polar solvent, (or ions which carry current). permeable because some of the proteins are channels that pass ions high capacitance concepts of resistance and capacitance will be dealt with shortly.

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20 Membrane signalling Lipid barrier to anything polar or big protein hormone or epinephrine (receptor). receptor is the GPCR Steroid hormones can go in It used to be thought that lipids just sit there. 1980's lipids turn over metabolically products of membrane lipid turnover are important mediators of intracellular signalling.

21 Signal transduction Hormone -> receptor protein (GPCR) -> G-protein -> cascade second messengers (IP 3 and DAG [diacyl glycerol from the membrane lipid PIP 2 [phosphatidylinositol-4,5-bisphosphate], note that calcium ion Ca 2+ ) becomes a next messenger in the cascade.

22 Phosphoinositide signalling Phospholipase C IP 3 is a "ligand" for a calcium channel. Ca2+ is sequestered in smooth ER. Inside cistern is tantamount to outside cell. Ca2+ is high outside, low inside, like Na+ unless deliberately increased intracellularly. Ca2+ levels are so important that 3 hormones regulate blood Ca2+, parathormone, calcitonin and vitamin D.

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24 Nicotinic receptor Acetylcholine - ligand (neurotransmitter), nicotine is a pharmacological agonist. receptor is a channel gives membrane electrical conductance [g]) Channel is ligand gated. pore in membrane can be open or closed. Sodium, higher outside cell, is likely to go in. Potassium, high inside cell is likely to go out.

25 Nobel Prize work 1991 ERWIN NEHER and BERT SAKMANN; patch clamping - electrical recording from single channels SIR JOHN CAREW ECCLES, SIR ALAN LLOYD HODGKIN and SIR ANDREW FIELDING HUXLEY voltage gated channels of the axon's action potential and worked on the neurotransmitter gated channels at synapses. In summary, ion channels are pretty fundamental.

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33 Membrane transport bulk transport: phagocytosis - cell eating pinocytosis - cell drinking Receptor mediated endocytosis clathrin coated pits turn to vesicles Receptor mediated endocytosis is important in clearing lipoproteins, LDL and HDL, from blood, and, of course, a receptor protein in the membrane is important in the transport

34 In summary (proteins) (1) transport (2)enzymes are on the membrane (3) receptors for hormones, neurotransmitters and developmental signals (4) cells are joined by proteins (5) cells communicate by proteins (6) cells hook to extracellular proteins by proteins

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