CELL MEMBRANE CHEMICAL COMPOSITION STRUCTURE AND MEMBRANE DYNAMICS

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CELL MEMBRANE : CHEMICAL COMPOSITION , STRUCTURE AND MEMBRANE DYNAMICS Presenter: Dr. Dnyanesh Amle

CELL MEMBRANE : CHEMICAL COMPOSITION , STRUCTURE AND MEMBRANE DYNAMICS Presenter: Dr. Dnyanesh Amle Moderator: Dr. Smita Kaushik

 • Boundaries of all the cells are defined by biological membrane • Barrier

• Boundaries of all the cells are defined by biological membrane • Barrier with selective permeability

COMMON PROPERTIES: • Sheet like structures • Contains mainly lipids and proteins • Membrane

COMMON PROPERTIES: • Sheet like structures • Contains mainly lipids and proteins • Membrane lipids are small amphipathic molecules • Specific proteins mediate distinctive function

COMMON PROPERTIES: • Non covalent assemblies • Asymmetric • Fluid structures • Electrically polarized

COMMON PROPERTIES: • Non covalent assemblies • Asymmetric • Fluid structures • Electrically polarized

 • FUNCTIONS: – Maintenance of cell shape – Cellular movements – Controls movement

• FUNCTIONS: – Maintenance of cell shape – Cellular movements – Controls movement of molecules between inside and outside of the cell – Cell-cell recognition and communication

 • MAINLY COMPOSED OF : – Lipids – Proteins – Carbohydrates

• MAINLY COMPOSED OF : – Lipids – Proteins – Carbohydrates

 • LIPIDS : – Phospholipids – Glycolipids – Cholesterol

• LIPIDS : – Phospholipids – Glycolipids – Cholesterol

1) PHOSPHOLIPIDS • Based on the platform: – Glycerophospholipids( Phosphoglycerides) – Sphingolipids

1) PHOSPHOLIPIDS • Based on the platform: – Glycerophospholipids( Phosphoglycerides) – Sphingolipids

PHOSPHOGLYCERIDES HYDROPHOBIC PART FATTY ACID G L Y C E R O L HYDROPHILIIC

PHOSPHOGLYCERIDES HYDROPHOBIC PART FATTY ACID G L Y C E R O L HYDROPHILIIC PART PHOSPHATE ALCOHOL

PHOSPHOGLYCERIDES • phosphatidate (diacylglycerol 3 -phosphate), the simplest phosphoglyceride • Major phosphoglycerides are derivatives

PHOSPHOGLYCERIDES • phosphatidate (diacylglycerol 3 -phosphate), the simplest phosphoglyceride • Major phosphoglycerides are derivatives of phosphatidate

 • Phosphtidylinositol: – Golgi body – Endosomes – Plasma membrane • Cardiolipin: –

• Phosphtidylinositol: – Golgi body – Endosomes – Plasma membrane • Cardiolipin: – Inner mitochondrial membrane • Phosphtidylcholine > Phosphtidylethanolamine • Plasmalogens: – Nervous tissue – Heart

SPHINGOLIPIDS • Derived from sphingosine SS P H I N G O S I

SPHINGOLIPIDS • Derived from sphingosine SS P H I N G O S I N E FATTY ACID PHOSPHATE • Ceramide ALCOHOL

2)GLYCOLIPIDS: • In animal cells: derived from sphingosine • Sugar unit is attached to

2)GLYCOLIPIDS: • In animal cells: derived from sphingosine • Sugar unit is attached to primary -OH group • Simple glycolipid : cerebroside – Phrenosine • Complex glycolipid: Ganglioside

 • Galactocerebroside: – Brain and nervous tissue • Glucocerebroside: – Non neural tissue

• Galactocerebroside: – Brain and nervous tissue • Glucocerebroside: – Non neural tissue • Ganglioside: – 5 -8% lipid in brain

3)CHOLESTEROL: • Third major membrane lipid

3)CHOLESTEROL: • Third major membrane lipid

OH

OH

 • MEMBRANE LIPIDS : AMPHIPATHIC MOLECULES Sphingo lipids glycero Phospho lipids Cholesterol SHORTHAND

• MEMBRANE LIPIDS : AMPHIPATHIC MOLECULES Sphingo lipids glycero Phospho lipids Cholesterol SHORTHAND DEPICTION

AMPHIPATHIC NATURE: • Micelles • Bilayer: leaflets

AMPHIPATHIC NATURE: • Micelles • Bilayer: leaflets

PROPERTIES OF LIPID BILAYER: • Formation in aqueous environment is rapid and spontaneous •

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

HYDROPHOBIC INTERACTIONS: • Inherent tendency to be extensive • Tend to close on themselves:

HYDROPHOBIC INTERACTIONS: • Inherent tendency to be extensive • Tend to close on themselves: forms compartments • Self sealing: As hole in lipid bilayer is energetically unfavorable

 • Type of structures formed depends on: – Fatty acyl chains – Degree

• Type of structures formed depends on: – Fatty acyl chains – Degree of saturation – Temperature

 • LIPOSOMES: sonicating Gel filtration

• LIPOSOMES: sonicating Gel filtration

Uses – To study the effect of different fatty acids on membranes – Drug

Uses – To study the effect of different fatty acids on membranes – Drug delivery – Concentrate in regions of increased blood flow : Cell gating – Selective fusion

MEMBRANE PROTEINS: • Integral • Peripheral • Amphitropic

MEMBRANE PROTEINS: • Integral • Peripheral • Amphitropic

INTEGRAL MEMBRANE PROTEINS : Inside Outside

INTEGRAL MEMBRANE PROTEINS : Inside Outside

PERIFERAL MEMBRANE PROTEINS : Cytoplasmic side Phosphtidylinositol Membrane Anchored protein _____ +++++++

PERIFERAL MEMBRANE PROTEINS : Cytoplasmic side Phosphtidylinositol Membrane Anchored protein _____ +++++++

 • Membrane proteins structure – Electron microscopy and X-ray crystallography • Membrane spanning

• Membrane proteins structure – Electron microscopy and X-ray crystallography • Membrane spanning α helix BACTERIORHODOPSIN

GLYCOPHORIN: • A protein containing single trans-membrane α helical strand • Present in plasma

GLYCOPHORIN: • A protein containing 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

74 95 GLYCOPHORINE

74 95 GLYCOPHORINE

 • A channel can be formed from β strands PORINE

• A channel can be formed from β strands PORINE

PROSTAGLANDIN H 2 SYNTHASE: Prostaglandin H 2 synthase

PROSTAGLANDIN H 2 SYNTHASE: Prostaglandin H 2 synthase

CARBOHYDRATES: • Rarely exists as free component • Present as glycoprotein and glycolipid •

CARBOHYDRATES: • Rarely exists as free component • Present as glycoprotein and glycolipid • Always present on the outer side

BIOLOGICAL MEMBRANES DIFFER IN COMPOSITION: • Myelin: 18% protein , ↑ glycosphingolipids • Plasma

BIOLOGICAL MEMBRANES DIFFER IN COMPOSITION: • Myelin: 18% protein , ↑ glycosphingolipids • Plasma membrane : 50% protein • Inner mitochondrial membrane : 75% protein, ↑ cardiolipins

FLUID MOSAIC MODEL: 1972 • S Jonathan Singer & Girth Nicolson • Membranes are

FLUID MOSAIC MODEL: 1972 • S Jonathan Singer & Girth Nicolson • Membranes are two dimensional solution of lipids and globular proteins CARBOHYDRATES INTEGRAL PROTEINS PERIFERAL PROTEINS LIPIDS

MEMBRANE DYNAMICS • ↓ physiological temp. : gel phase • ↑ physiological temp. :

MEMBRANE DYNAMICS • ↓ physiological temp. : gel phase • ↑ physiological temp. : liquid-disordered state • Intermediate temp. : liquid-ordered state • Unsaturated fatty acids • Cholesterol

LATERAL DIFFUSION: • Biological membranes are not rigid structures • Lipids > proteins are

LATERAL DIFFUSION: • Biological membranes are not rigid structures • Lipids > proteins are constantly in a lateral motion • Can be detected by FRAP • S = (4 Dt)1/2 • For lipid : D= 1µm 2/s • S= 2 µm/S

 • Proteins differ extremely in mobility – Rhodopsin : D=0. 4 µm/s –

• Proteins differ extremely in mobility – Rhodopsin : D=0. 4 µm/s – Fibronectin : D = 10 -2µm/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

TRANSVERSE DIFFUSION: • Flip flop occurs once in several hours • Flip flop of

TRANSVERSE DIFFUSION: • Flip flop occurs 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

Cytosolic leaflet

Cytosolic leaflet

MEMBRANE FLUIDITY : CLINICAL CORRELATION • ↑cholesterol : alteration in membrane fluidity • Spur

MEMBRANE FLUIDITY : CLINICAL CORRELATION • ↑cholesterol : alteration in membrane fluidity • Spur cell anemia • Alcohol intoxication • Abetalipoproteinemia: ↑ sphingomyeline ↓phosphatidylcholine • Lecithin cholesterol acyltransferase deficiency • Hypertension • Alzheimer’s

MEMBRANES : ASYMMETRIC STRUCTURE • Inside-outside asymmetry: – Phospholipids – Proteins – Carbohydrates •

MEMBRANES : ASYMMETRIC STRUCTURE • Inside-outside asymmetry: – Phospholipids – Proteins – Carbohydrates • Regional asymmetry • Mechanism

MICRO DOMAINS OF LIPID PROTEIN COMPLEX • Micro domain called lipid raft contains distinctly

MICRO 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 microdomains

 • Outer leaflet : ceramid and glycosphogilipids with long chain fatty acids →

• Outer leaflet : ceramid and glycosphogilipids with long chain fatty acids → thicker • Inner leaflet ↑ saturated fatty acids → closed packing

 • Function : to segregate and concentrate specific protein and to facilitate their

• 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

CAVEOLAE: • Caveoline cholesterol binding integral membrane protein • Forces bilayer to curve inwards

CAVEOLAE: • Caveoline cholesterol binding integral membrane protein • Forces bilayer to curve inwards forming caveolae • Functions : membrane trafficking, signal transduction Caveoline dimer with six fatty acid moeitis

MEMBRANE CURAVATURE : • Central to ability of membrane to undergo fusion with other

MEMBRANE CURAVATURE : • 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

FUSION OF SYNAPTIC VESICLE: • v-SNARES • t-SNARES • SNAP-25 • NSF V-SNARE SNAP-25

FUSION OF SYNAPTIC VESICLE: • v-SNARES • t-SNARES • SNAP-25 • NSF V-SNARE SNAP-25 t-SNARE

TRANSFERRIN RECEPTOR CYCLE: Transferrin receptor cycle

TRANSFERRIN RECEPTOR CYCLE: Transferrin receptor cycle

IN A NUTSHELL • Biological membranes define cellular boundaries, divide cells into discrete compartments,

IN A 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.

 • Lipid > proteins are continuously in a state of motion in the

• 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

THANK YOU

THANK YOU

HYDROPATHY PLOT GLYCOPHORINE

HYDROPATHY PLOT GLYCOPHORINE

STEPS IN FUSION: • Recognition • Close opposing • Local disruption • Fusion proteins

STEPS IN FUSION: • Recognition • Close opposing • Local disruption • Fusion proteins

TIGHT JUNCTION: • Present between two cells that lies in close a approximation •

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: provide attachment of cells to the basal tissue • Mostly seen in epithelial cells