Cell Membrane

CELL MEMBRANE

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Properties of cell membrane 2. Chemistry structures of membrane lipids 3. Fluid-mosaic model of plasma membrane 4. Clinical manifestations on the basis of certain membrane dysfunctions 1.

Prof. K.M. Chan, Biochemistry, Rm513B, BMSB. Email: [email protected]; Tel: 3163-4420.

Lipids are water insoluble and amphipathic in nature. hydrophobic hydrophilic

A liposome formed with lipid bilayer:

water Lipid on the surface of water

Lipid bilayer

Bubbles with soap trapping a layer of water inside; with the detergents at the outside (just the reverse of the lipid bilayer of plasma membrane). hydrophobic hydrophilic hydrophilic

water

water

hydrophobic

1. Properties of plasma membrane 

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Sheet-like (layer) structure consists of proteins, lipids, with carbohydrates attached to proteins or lipids outside of the membrane. Non-covalent assemblies of lipids and proteins. The lipid molecules are amphi-pathic molecules, they have both hydrophilic (polar) and hydrophobic (nonpolar) moieties. Barriers to the flow of charged molecules and large molecules. Mainly hydrophobic or lipid soluble molecules can go through. Transmembrane proteins serve as transporters, channels, enzymes, signal transducers, etc.

1.1 Plasma membranes 

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Membranes are held up with van der Waal’s force and hydrophobic interaction with no covalent interactions among molecules, therefore they can fuse together and break up by hydrophobic interactions. These membrane fusion processes are mainly controlled by peripheral proteins underneath the membrane. Budding, endocytosis and exocytosis are common membrane movements by membrane fusion. By membrane fusion, Golgi complex and move proteins to vesicles and surface membrane. Secretory proteins can be bound with vesicles and released out of the cells. The mitochondrion has 2 layers of membrane, the inner is similar to their descendant of prokaryotes, the outer from eukaryotes; indicating its symbiotic origin.

1.2 Fatty acids and phospholipids  Membranes

have three kinds of lipids: phospholipids, glycolipids, & cholesterol  Fatty acids (FAs) form the basic structures of phospholipids and glycolipids  Saturated FAs VS Unsaturated FAs  Strong van der waals interaction between the non-polar hydrocarbon regions of the molecules

Common saturated fatty acids Structure Hydrophobic hydrocarbon (alipathic) tail

Common Name

Systematic Name

Abbreviation

Capric

n-Decanoic

10:0

CH3(CH2)8COOH

Lauric

n-Dodecanoic

12:0

CH3(CH2)10COOH

Myristic

n-Tetradecanoic

14:0

CH3(CH2)12COOH

Palmitic

n-Hexadecanoic

16:0

CH3(CH2)14COOH

Stearic

n-Octadecanoic

18:0

CH3(CH2)16COOH

Arachidic

n-Eicosanoic

20:0

CH3(CH2)18COOH

Behenic

n-Docosanoic

22:0

CH3(CH2)20COOH

Lignoceric

n-Tetracosanoic

24:0

CH3(CH2)22COOH

Cerotic

n-Hexacosanoic

26:0

CH3(CH2)24COOH

Common unsaturated fatty acids Common Name

Systematic Name

Abbreviation

Structure Hydrophobic hydrocarbon (alipathic) tail

Palmitoleic

cis-9Hexadecenoic

16:1c∆9

CH3(CH2)5CH=CH(CH2)7COOH

Oleic

cis-9Octadecenoic

18:1c∆9

CH3(CH2)7CH=CH(CH2)7COOH

Linoleic

Cis,cis-9,12Octadecadienoic

18:2c∆9,12

CH3(CH2)4CH=CHCH2CH=CH(CH2)7COOH

Linolenic

All-cis-9,12,15Octadecadienoic

18:3c∆9,12,15

CH3CH2CH=CHCH2CH=CHCH2CH=CH(CH2)7C OOH

Arachidonic

All-cis-5,8,11,14Eicosatetraenoic

20:4c∆ 5,8,11,14

CH3(CH2)4CH=CHCH2CH=CHCH2CH=CHCH2C H=CH(CH2)3COOH

Melting points of saturated fatty acids increase with increasing molecular weight; melting points of unsaturated fatty acids are determined by the number of double bonds (cis C=C bonds rotate 120 O).

Changes from a gel state to a liquid state at special melting temperature 20

80 70 60

The melting points of saturated fatty acid increase with increasing molecular weight

50 40

Melting Point ºC

Melting Point ºC

90

10 0 -10 -20

30 8 10 12 14

18

22

26

28

Number of carbon

1

2

3

4

Number of double bonds

1.3 structure of lipid bilayer and phospholipids Phospholipid molecule

Hydrophobi c fatty acid tails

Phosphat e Glycerol Fatty acid(unsaturate d)

Fatty acid (saturated)

Hydrophobic core of lipid bilayer

Hydrophilic head

Polar group

Hydrophili c head on surface

Fatty acids (FAs) form the basic structures of phospholipids

Hydrophilic head to cytoplasm

Lipid bilayer at work: [1] melting points affect the fluidity, [2] hydrophobic actions form the membrane. Loosely packed: higher fluidity

Tightly packed: more rigid and lower fluidity

Increase of temperatur e

Explain why and how a detergent can kill germs?? Why bleach and alcohol can kill bacteria and viruses??

2. Chemical Structures of Membrane lipids Comparison of storage lipids (neutral) and membrane lipids (polar) with Glycerophospholipids and Sphingolipids (including glycolipids) Triacylglycerols, storage lipids (neutral)

POLAR MEMBRANE LIPIDS Phospholipids: Glycolipids: Phospholipids: GlyceroShingolipids Shingolipids phospholipids (neutral)

Polysaccharide Fatty acid

Phosphate

Glycerol

Polar head group

Sphingosine Monosaccharide

Adapted from Nelson and Cox, 2000. Lehninger Principles of Biochemistry. Worth Pub.Co.

2.1 Glycerophospholipids and sphingolipids  Different

ways of putting two fatty acid chains together as major phospholipids on membrane  Glycerophospholipids with GLYCEROL linkage, e.g. phosphatidyl choline or serine.  Sphingolipids are derived from sphingosine, e.g. sphingomyelin, which has no glycerol linkage.

Glycero-phospholipids

Shingolipids

2.2 Sphingomyelins, forming a ceramide first by adding a fatty acid chain, e.g. Sphingolipid as a major component of nerve cells

Sphingosine

2.3Glycolipids: Cerebrosides (e.g. Sphinoglycolipids)

Ceramide

Gangliosides: 6% of brain lipids, ceramide oligosaccharides with sialic acid residue(s), excellent for recognition by antibodies.

2.4 Cholesterol stays in between fatty acids with its rigid planar steroid ring and affect membrane fluidity Polar Head Polar Head

Phosphat e Glycerol Fatty acid(unsaturate d) Hydrophobi c fatty acid tails

Non polar hydrocarbon Tail

Bacterial cells do not have cholesterol, neither in mitochondria too.

3. The Fluid-Mosaic Model (Singer and Nicolson, 1972): • Amphipathic lipids form a bilayer stabilized by the hydrophobic interaction. • The lipid bilayer is a fluid-like structure, with fluidity regulated by the number of double bonds in the fatty acids (increasing unsaturation increases fluidity) and cholesterol content (increasing cholesterol decreases fluidity). • The components of membranes with lipids and proteins are asymmetrically oriented: the two faces are different.

3.1 The Fluid-Mosaic Model (cont’) 4. The proteins and the components are free to move laterally (lateral movement allowed), but no or little flip-flopping allowed (flippase or transporter is needed.  The lipid bilayer forms a permeability barrier to polar molecules which can only cross the membrane by a specific method via membrane proteins: permeases, channel, or transporters)  Clustering, capping of lipids or proteins on cell surface also exist (not really random)

3.2 The asymmetrical nature of plasma membrane: polar heads of phospholipids and carbohydrates of glycolipids vary on two sides of the lipid bilayer; protein orientations also vary and are fixed too. carbohydrates Cell Wall

Lipid bilayer

Peripheral proteins

Cytoskeleton below may control these transmembrane proteins

Rotations occur

Integrated Protein (NO flip-flopping)

Lateral transport modes on the cell surface: A. Transient confinement by Obstacle clusters; B. by Cytoskeleton; C. Directed motion; D. Random Diffusion.

B

D

A Lipid raft exists

C

Adapted from Jacobson et al, 1995, Revisiting the fluid mosaic model of membranes. Science 268:1441-1442.

3.4 Possible ways of proteins stay with the plasma membrane (1)Trans-membrane

(2) Lipoproteins

(3) Protein attached N

C

C

C C

C

N N

Lipid bilayer

βbarrel

N

C

Trans-membrane proteins must have hydrophobic region, usually helical bundles, to get into the membrane’s core hydrophobic region: hydrophobic interactions.

N N

C

N

Adapted from Alberts et al., 1998. Essential Cell Biology. An Introduction Biology of the Cell. Garland Pub.Inc.

4. Clinical Correlations 

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Snake venom contains phospo-lipase which removes fatty acid from phosphatidylcholine on membrane, causing hemolysis of red cells to leak red cell contents into the plasma and leading to blood clotting and swollen of limbs (edema). Ankyrin and or spectrin deficiency can cause anemia. Red cells are disrupted without the peripheral proteins to hold the membrane. Human Immunodeficiency Virus enters the cells like other viruses on their specific cell surface proteins. HIV binds gp120 , with CD4 and CCR5, on the target T cell. Membrane consists of amphipathic compounds, many drugs or toxins (e.g. antibiotics) are amphipathic compounds to perturb membrane structure and work as detergent to disrupt or break-up the lipid bilayer.

Final remarks:   

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Chemical properties of fatty acids are essential to the structure and function of plasma membranes. Cholesterol and fatty acid composition are key fluidity regulator of cell membrane. Fluid-mosaic model of membrane is well established: proteins embedded in lipid bilayer. Orientations of the membrane is fixed, no flip-flopping. Proteins are responsible for most if not all the major cellular functions (homeostasis) of cell membranes. Integral proteins get into the cell membrane with their hydrophobic transmembrane domains which consist of helical bundles spanning through the membrane. Visit www.cmbio.blogfa.com