“Bone spicule” appearance of peripheral retina- abnormal, pigment containing cells-not actual boneRemember James ..1. The doctor noticed pigment deposits (bone spiculepattern) in the periphery of James’ retina.Remember .2. The doctor thought James’ electroretinogramwas slightly unusual.Remember ..3. The doctor thinks James has a degree of night blindness as well as defective peripheral visionThe typical cell –a building blockThe term cell was first used by Robert Hooke 1635-1703.Hooke examined very thin slices of cork and saw what looked like the walled compartments of a honeycomb. Hooke called the structures cells.Hooke’s microscopeCorneal endotheliumCell Theory (simplified)1. Cells are the ‘building blocks’ ofanimals and plants2. Cells arise from pre-existing cells3. Cells are the smallest unit having all thefunctions of living systems4. Homeostasis of higher levels of biologicalorganization arises from coordinated activity of cellsCommon cell Structures•Plasma membrane (cell membrane)•Nucleus -contains genetic material•Cytoplasm: everything between the membrane and the nucleus–cytosol = aqueous intracellular fluid, electrolytes and other dissolved solutes–organelles = subcellular structures with specific functionsOrganellesMembranousNucleusMitochondrionEndoplasmic reticulumLysosomePeroxisomeNon membranousRibosomeProteasomeCytoskeletonThe Typical CellFirst, how big is a typical cell? .Surface area is large when a structure is built from many small cellsCell shape affects the surface to volume ratio. .. the flat cell shown here has the same volume as the cube but a larger surface areaCELL SHAPE MATTERSThe cell surface is biological membraneWhat do we need to know? ..made from lipids, proteins & carbohydrates!!!!!SPECIAL OFFER!!!!!PLASMA MEMBRANEKeeps organelles in! (No worries about losing your nucleus)Protection from the outside world.Customized to your own cell type.Latches onto most extracellular matrix.Every cell needs one!BE RECOGNIZED – GET A PLASMA MEMBRANE TODAY! Live up to your “potential”with a plasma membrane!Plasma membrane job duties include .•Barrier•Shipping and receiving for cell•Security checkpoint•Identification•Communication with other cellsA. Gorter & Grendel 1926B. Davson & Danielli 1943C. Singer 1972. Fluid mosaic modelD. Contemporary model showing integral and peripheral proteinsAs research progresses our view of the plasma membrane has changedLipid Composition1. Phosphoglycerides (also called glycerophospholipids or simply phospholipids)2. Sphingolipids3. Sterols (eg cholesterol)‘Amphipathic Structure’includes polar (‘head group’) andnon-polar (‘tail’) regionsLipid Bilayer Composition1. Phosphoglycerides (phospholipids)•Amphipathic•Main lipid constituent of plasma membrane•Glycerol backbone + 2 fatty acyl tails in ester linkage + a polar head group (a phosphate ester of another alcohol like choline, ethanolamine, serine or inositol).Lipid Bilayer Composition2. Sphingolipids•AmphipathicSphingosine backbone (1 tail) + 1 fatty acid tails in amide + a polar head group, either a carbohydrate or a phosphate ester of another alcohol like choline or ethanolamine.glycosphingolipids (gangliosides)phosphosphingolipids (sphingomyelins)Phospholipids naturally assemble in a way that “hides” the hydrophobic tail from waterSelfassemblyH2OH2OLIPID56 nm(50 – 60 ÅPhosphatidylcholine bilayerLipid Bilayer Composition3. Cholesterol•Amphipathic•Sterol•Receives a lot of bad press but is an essential membrane component•Wedges into bilayer and has effect on fluidity by interacting with first few hydrocarbon groups on phospholipid tailsrotationlateral diffusion~1-2 um/sec~20 x 109/secMolecules move in the bilayerAn unsaturated fatty acid has one or more double bonds.Membrane fluidity•Depends on lipid composition•Fatty acid chain length– longer means tighter packing of tails and less fluid•Number of double bonds in fatty acid chain –more double bonds means looser packing of tails and more fluid•Cholesterol alters fluidityLet’s consider the “Barrier” function of membranesfree diffusive flux of H2O“Concentration” of H2Oin the “pure water is 55.5 M“Concentration” of H2Oin the lipid bilayer is ~0.005 MThe presence of the bilayer reduces the freediffusive flux of H2O about 10,000-fold!Let’s consider the “Barrier” function of membranesThe cell does not need a the plasma membrane to be a completely sealed barrierProteins in biological membranes act as selective and well controlled channels, pumps and transportersWhat do we need to know?peripheralintegralTwo Categories: Integral & PeripheralMembrane ProteinsHydrophilic region Hydrophilic regionHydrophobic regionHydrophobic regionIntegral membrane proteinsTransporters pumps and channels in the plasma membrane regulate cytopasmic solute composition.Transmembrane proteins anchor the cytoskeleton to extracellular matrix or neighboring cells.Proteins and carbohydrates give the plasma membrane specific characteristics and distinguish one cell from another.Some proteins are almost always present -eg Na,K-ATPaseSome proteins are only found in specialized cells -eg voltage sensitive sodium channelsPoints to consider:The inner and outer surfaces of the plasma membrane are very different, both in terms of function and in terms of the phospholipid and protein (or parts of proteins) that face inward and outward.Many membrane proteins are not distributed randomly across the cell surface. Instead they are localized in a specific pattern.Later we’ll see how proteins are directed, sorted and tethered .The plasma membrane is a site where certain proteins are brought together to make specificenzyme reactions possible.Receptors on the plasma membrane sense the presence of extracellular insulin, neuropeptides and hormonesWhat about the eye?Rhodopsin is an integral membrane protein expressed in rod photoreceptorsPhotoreceptors are easily recognized in sections of retina .Fariss et al 2000 Am J Ophthalmol129:215We know rhodopsin is a rod photoreceptor protein because antibodies to rhodopsin localize to the rod cells (green color in lower panel)How do we know that? .Immunolocalization of rhodopsin in a normal human retina (right) and the retina of an individual who has a form or retinitis pigmentosa (left).Fully formed rod outer segments (*) are