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Cell membrane 93 2010
The cell membrane is composed mainly of lipids and proteins that form a fluid bilayer. Phospholipids are the major lipids and form a bilayer with their hydrophobic tails facing inward and hydrophilic heads facing outward. Membrane proteins can be integral or peripheral. The fluid mosaic model describes membranes as a fluid bilayer with proteins diffusing laterally. Membranes exhibit asymmetry, fluidity, and formation of microdomains. Specific proteins mediate membrane fusion and curvature essential for cellular processes.
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Cell membrane 93 2010
- 1. CELL MEMBRANE :CELLMEMBRANE : CHEMICAL COMPOSITION ,CHEMICAL COMPOSITION , STRUCTURE AND MEMBRANESTRUCTURE AND MEMBRANE DYNAMICSDYNAMICS Presenter: Dr. Dnyanesh Amle Moderator: Dr. Smita Kaushik
- 2. • Boundaries ofall the cells are defined byBoundaries of all the cells are defined by biological membranebiological membrane • Barrier with selective permeabilityBarrier with selective permeability
- 4. COMMON PROPERTIES:COMMON PROPERTIES: •Sheet like structures • Contains mainly lipids and proteins • Membrane lipids are small amphipathic molecules • Specific proteins mediate distinctive function
- 5. COMMON PROPERTIES:COMMON PROPERTIES: •Non covalent assemblies • Asymmetric • Fluid structures • Electrically polarized
- 6. • FUNCTIONS:FUNCTIONS: – Maintenanceof cell shape – Cellular movements – Controls movement of molecules between inside and outside of the cell – Cell-cell recognition and communication
- 7. • MAINLY COMPOSEDOF :MAINLY COMPOSED OF : – Lipids – Proteins – Carbohydrates
- 8. • LIPIDSLIPIDS : –Phospholipids – Glycolipids – Cholesterol
- 9. 1) PHOSPHOLIPIDS1) PHOSPHOLIPIDS •Based on the platform: – Glycerophospholipids( Phosphoglycerides) – Sphingolipids
- 10.
- 11. PHOSPHOGLYCERIDESPHOSPHOGLYCERIDES • phosphatidate (diacylglycerol3-phosphate), the simplest phosphoglyceride • Major phosphoglycerides are derivatives of phosphatidate
- 12. • Phosphtidylinositol: – Golgibody – Endosomes – Plasma membrane • Cardiolipin:Cardiolipin: – Inner mitochondrial membrane • Phosphtidylcholine > Phosphtidylethanolamine • Plasmalogens:Plasmalogens: – Nervous tissue – Heart
- 13. SPHINGOLIPIDSSPHINGOLIPIDS • Derived fromsphingosine • Ceramide SS P H I N G O S I N E FATTY ACID ALCOHOLPHOSPHATE S P H I N G O S I N E
- 14. 2)GLYCOLIPIDS:2)GLYCOLIPIDS: • In animalcells: derived from sphingosine • Sugar unit is attached to primary -OH group • Simple glycolipid : cerebroside – PhrenosinePhrenosine • Complex glycolipid: Ganglioside
- 15. • Galactocerebroside: – Brainand nervous tissue • Glucocerebroside: – Non neural tissue • Ganglioside: – 5-8% lipid in brain
- 16. 3)CHOLESTEROL:3)CHOLESTEROL: • Third majormembrane lipid
- 17.
- 18. • MEMBRANE LIPIDS: AMPHIPATHIC MOLECULESMEMBRANE LIPIDS : AMPHIPATHIC MOLECULES Sphingo lipids glycero Phospho lipids Cholesterol SHORTHAND DEPICTION
- 19. AMPHIPATHIC NATURE:AMPHIPATHIC NATURE: •Micelles • Bilayer: leaflets
- 20. PROPERTIES OF LIPIDBILAYER:PROPERTIES OF LIPID BILAYER: • Formation in aqueous environment is rapid and spontaneous • Hydrophobic interactions: major driving force • Other forces: – Van der waal’s attractive forces – Electrostatic – Hydrogen bonds • Co-operative structures
- 21. HYDROPHOBIC INTERACTIONS:HYDROPHOBIC INTERACTIONS: •Inherent tendency to be extensive • Tend to close on themselves: forms compartments • Self sealing: As hole in lipid bilayer is energetically unfavorable
- 22. • Type ofstructures formed depends on: – Fatty acyl chains – Degree of saturation – Temperature
- 23.
- 24. Uses – To studythe effect of different fatty acids on membranes – Drug delivery – Concentrate in regions of increased blood flow : Cell gatingCell gating – Selective fusion
- 25. MEMBRANE PROTEINS:MEMBRANE PROTEINS: •Integral • Peripheral • Amphitropic
- 26. Inside Outside INTEGRAL MEMBRANEPROTEINS :INTEGRAL MEMBRANE PROTEINS :
- 27. +++++++_ _ __ _Phosphtidyl- inositol Membrane Anchored protein Cytoplasmic side PERIFERAL MEMBRANE PROTEINS :PERIFERAL MEMBRANE PROTEINS :
- 28. • Membrane proteinsstructure – Electron microscopy and X-ray crystallography • Membrane spanning α helix BACTERIORHODOPSIN
- 29. GLYCOPHORIN:GLYCOPHORIN: • A proteincontaining single trans-membrane α helical strand • Present in plasma membrane of human erythrocytes • Amino terminus exterior to cell contains various oligosaccharide unit including ABO and MN blood group determinants
- 30.
- 31. • A channelcan be formed from β strands PORINE
- 33. Prostaglandin H2 synthase PROSTAGLANDINHPROSTAGLANDIN H22 SYNTHASE:SYNTHASE:
- 34. CARBOHYDRATES:CARBOHYDRATES: • Rarely existsas free component • Present as glycoprotein and glycolipid • Always present on the outer side
- 35. BIOLOGICAL MEMBRANES DIFFERINBIOLOGICAL MEMBRANES DIFFER IN COMPOSITION:COMPOSITION: • Myelin: 18% protein , ↑ glycosphingolipids • Plasma membrane : 50% protein • Inner mitochondrial membrane : 75% protein, ↑ cardiolipins
- 36. FLUID MOSAIC MODEL:FLUIDMOSAIC MODEL: 1972 • S Jonathan Singer & Girth Nicolson • Membranes are two dimensional solution of lipids and globular proteins CARBOHYDRATES LIPIDS PERIFERAL PROTEINS INTEGRAL PROTEINS
- 37. MEMBRANE DYNAMICSMEMBRANE DYNAMICS •↓ physiological temp. : gel phase • ↑ physiological temp. : liquid-disordered state • Intermediate temp. : liquid-ordered state • Unsaturated fatty acids • Cholesterol
- 38. LATERAL DIFFUSION:LATERAL DIFFUSION: •Biological membranes are not rigid structures • Lipids > proteins are constantly in a lateral motion • Can be detected by FRAP • S = (4Dt)1/2 • For lipid : D= 1µm2 /s • S= 2 µm/S
- 39. • Proteins differextremely in mobility – Rhodopsin : D=0.4 µm/s – Fibronectin : D = 10-2 µm/s • fluidity increases with increase in – No of short chain fatty acids – Unsaturated fatty acids – Temperature • Cholesterol decreases fluidity at high temp • Increases fluidity at low temp
- 40. • Flip flopoccurs once in several hours • Flip flop of proteins have not been observed • Thus proteins play important role in preserving the asymmetry of the membrane • But sometimes Flip-Flop is needed TRANSVERSE DIFFUSION:TRANSVERSE DIFFUSION:
- 41.
- 42. MEMBRANE FLUIDITY :CLINICAL CORRELATIONMEMBRANE FLUIDITY : CLINICAL CORRELATION • ↑cholesterol : alteration in membrane fluidity • Spur cell anemia • Alcohol intoxication • Abetalipoproteinemia: ↑ sphingomyeline ↓phosphatidylcholine • Lecithin cholesterol acyltransferase deficiency • Hypertension • Alzheimer’s
- 43. MEMBRANES : ASYMMETRICSTRUCTUREMEMBRANES : ASYMMETRIC STRUCTURE • Inside-outside asymmetry: – Phospholipids – Proteins – Carbohydrates • Regional asymmetry • Mechanism
- 44. MICRO DOMAINS OFLIPID PROTEIN COMPLEXMICRO DOMAINS OF LIPID PROTEIN COMPLEX • Micro domain called lipid raft contains distinctly organized bilayer structures • Enriched in sphingolipids and cholesterols •Biological membranes are actually mosaic of Different micro- domains
- 45. • Outer leaflet: ceramid and glycosphogilipids with long chain fatty acids → thicker • Inner leaflet ↑ saturated fatty acids → closed packing
- 46. • Function :to segregate and concentrate specific protein and to facilitate their activity • Proteins are activated when – several rafts fuse together – Ligands binding which favors fusion of rafts
- 47. CAVEOLAE:CAVEOLAE: • Caveoline cholesterolbinding integral membrane protein • Forces bilayer to curve inwards forming caveolae • Functions : membrane trafficking, signal transduction Caveoline dimer with six fatty acid moeitis
- 48. MEMBRANE CURAVATURE :MEMBRANECURAVATURE : • Central to ability of membrane to undergo fusion with other membrane • Mechanisms – Intrinsically curved protein binding – Many subunits of scaffold protein into proteins assembled into curved supra-molecular complexes – May insert one or more hydrophobic helices into one face of bilayer
- 49. FUSION OF SYNAPTICVESICLE:FUSION OF SYNAPTIC VESICLE: • v-SNARESv-SNARES • t-SNARESt-SNARES • SNAP-25SNAP-25 • NSFNSF V-SNARE t-SNARESNAP-25
- 50. Transferrin receptor cycle TRANSFERRINRECEPTOR CYCLE:TRANSFERRIN RECEPTOR CYCLE:
- 51. IN A NUTSHELLINA NUTSHELL • Biological membranes define cellular boundaries, divide cells into discrete compartments, organize complex reaction sequences, and act in signal reception and energy transformations. • The lipid bilayer is the basic structural unit explained by Fluid-mosaic model. • Membranes are structarally and functionally asymmetrical.
- 53. • Lipid >proteins are continuously in a state of motion in the plane of cell membrane called lateral diffusion • But transverse diffusion or Flip-flop of lipids is very slow except when specifically catalyzed by flippases,floppases and scramblases. • lipid rafts are rich in sphingolipids and cholesterol consist of membrane proteins that are GPI-linked • Specific proteins mediate the fusion of two membranes, which accompanies processes such as viral invasion and endocytosis and exocytosis
- 54.
- 55.
- 56. STEPS IN FUSION:STEPSIN FUSION: • Recognition • Close opposing • Local disruption • Fusion • Fusion proteins
- 57. TIGHT JUNCTION:TIGHT JUNCTION: •Present between two cells that lies in close a approximation • Forms narrow hydrophilic channels • Prevents the diffusion of macromolecules • Only three layers of plasma membrane are present DESMOSOMES:DESMOSOMES: provide attachment of cells to the basal tissue • Mostly seen in epithelial cells