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Chapter 3

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Content 3.1.sMembrane components and

structure of biomembranes 3.1.1. Membrane Lipid 3.1.2 Steroids 3.1.3. Membrane Protein 3.1.4. Membrane carbohydrate 3.1.5. Membrane Fluidity 3.1.6. Membrane asymmetry 3.1.6. Modals of cell 3.1.6. Common function of Membrane Membrane Cheng Xiaoli Zhengzhou University

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Membrane Basic Concepts All Cell surrounded by a layer of membrane contained special kind of lipids, proteins and sugars, called cell membrane. Some Cell such as plant cells and some bacteria cells, contain a cell wall in appearance of the plasma membrane, or contain a capsule surrounding the cell wall, or contain some special structures on the surface of plasma membrane, such as cell Cheng Xiaoli Zhengzhou University

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Membrane Basic Concepts

A living cell is a self-reproducing system of molecules hold inside a container. The container is the plasma membrane, which forms a dynamic interface between the cytosol and the environment. plasma membrane

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Membrane Basic Concepts In eukaryote cell, some membrane compartmentalize the cell into smaller subcompartments termed organelles, such as endoplasmic reticulum , vesicle , Golgi body , mitochondria , etc. each organelle surrounded by one or more layer of membrane. All this membrane form closed structures surrounded b y one or more layer of membrane System. The plasma membrane and cytoplasmic membrane

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3.1 Components and structure of biomembranes

Basic compositions of all membrane are lipids, proteins and a small quantity of saccharide.

3.1.1 Lipid

The cellular plasma and organelle membranes within your body contain 40% to 80% lipid. Among these lipids, the phospholipid are the most prevalent. Lipid contended in a typical biomembrane are phospholipids ( phosphoglycerides ) and steroids. All three classes of lipids are amphopathic molecules. Cheng Xiaoli Zhengzhou University

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Main Kinds of Membrane Lipid •Phosphatidylethanolamine(PE)

磷脂酰乙

醇胺

•Phosphatidylserine (PS)

磷脂纤丝氨

酸

•Phosphatidylcholine (PC) 卵磷脂 •Sphingomyelin (SM) 神经 ) 鞘磷 脂

•Cholesterol (CH)

胆固

醇

•Glycolipid (GL)

糖磷脂

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Lipid composition of some biomembranes Membrane RBC plasma membrane Liver plasma membrane Mitochondrial membrane Endoplasmic reticulum

PE

PS

PC SM

18 7 35 17

7 4 2 3

21 24 39 40

磷脂纤丝氨酸

CH Other

18 3 26 19 7 17 0 trace 3 5 trace 6

PE: phosphatidylethanolamine 磷脂酰乙醇胺 PS: phosphatidylserine

GL

13 22 21 27

GL: glycolipid PC: phosphatidylcholine

卵磷脂

SM: sphingomyelin

鞘磷脂

CH: cholesterol Cheng Xiaoli Zhengzhou University

Lipids Structure

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A typical phospholipid molecules consists of a amphipathic lipids, part watersoluble and part water-insoluble since they have both hydrophilic ( or water-loving) polar head groups and hydrophobic ( or

HO

hydrophilic head

O=P

CH 2

O CH CH 2

O

O

phosphate O-

glycerol

C=OC=O

hydrophobic tail

Fatty acid tail

Phosphatidic acid is the most simplistic PL. It is a promolecular to be linked with other molecular to form different PL Cheng Xiaoli Zhengzhou University

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Saturated and Unsaturated Fatty Acid Tail

CH CH2 .. … .

CH2 CH3

=

C=O CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2

….. .

•The fatty acid tail on the left is saturated , meaning that every carbon atom is linked to two or three hydrogen atoms. •The tail on the right is unsaturated , with a double bond between carbon atoms at the point indicated by the arrow.

CH2 O

CH2 N+ (CH3) 3 CH2 O O P =O O CH CH2 O C=O CH2 CH2 CH2 CH2 CH2 CH2

animated model

CH3

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Saturated and Unsaturated Fatty Acid Tail

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Bilayer structures • All kinds of phospholipid molecules in biomembrane contain a core or called “nonpolar tail” and a hydrophilic core or called “polar head”. This molecular character makes phospholipid have ability, in certain conditions, to form a spherical bilayer structures called liposome. • In fact, this is also the basic pattern of phospholipid in the natural biomembrane. The bilayer structures make up of basic framework of biomembrane.

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Effects of Variation in Phospholipid Fatty Acid Composition (a) If a lipid layer is composed entirely of saturated fatty acids, the fatty acid tails nest together to form rigid structures. (b) In unsaturated fatty acids, a double bond causes a deformation that interferes with the orderly stacking of the molecules and makes the fatty acid region more fluid. (c) When more double bonds are present, the deformations and resulting fluidity are greater still. Cheng Xiaoli Zhengzhou University

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Effects of Variation in Phospholipid Fatty Acid Composition

Tight-knit Form

Full of Free Space Form

• On the nature of the hydrocarbon tails: the closer and more regular the packing of the tails, the more viscous and less fluid the bilayer will be. Cheng Xiaoli Zhengzhou University

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G lycolipid Glycolipids: like phospholipids, these compounds are composed of a hydrophobic region, containing two hydrocarbon tails, and a polar region, which, however, contains one or more sugar residues and no phosphate. Sugar residues chain

Polar head nonpolar tail Cheng Xiaoli Zhengzhou University

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Glycolip id Glycolipid are more minor components of human and

other animal membranes. Sugar residues of plasma membrane glycolipids almost always face the outside of the cell; that is, they have an asymmetric distribution, being found only in the outer leaflet of the bilayer.

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3.1.2 Steroids • Steroids include cholesterol and certain hormones.

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Cholesterol is a common component of animal cell membranes.

• Cholesterol molecules intersperse among phospholipid tails in the bilayer or filled spaces between neighboring phospholipid molecules that are caused by the kinks in phospholipid molecules unsaturated hydrocarbon tails. In this way cholesterol stiffens the bilayer and makes it less fluid and less permeable. Cheng Xiaoli Zhengzhou University

3.1.2 Steroids Cholesterols is amphiphathic because its hydroxyl

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group can interact with water. And Cholesterols is a saturated molecule, without double bond between carbon atoms . HO polar head

CH3 CH3 CH

rigid planar steroid ring structure

CH3 CH 2 CH2 CH2

Nonpolar (hydrocarbon) hydrocarbon tail

H3C CH CH3

animated model

cholesterolCheng formula Xiaoli

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• Cholesterol has a number of functions • It is a structural component of cell membranes. The ratio of cholesterol to polar lipids affects the stability, permeability, and protein mobility of a membrane. Membranes with high ratios have high stability and relatively low permeability; their major function is a protective barrier. • Cholesterol is stored in the adrenals, testes, and ovaries, chiefly as the fatty acid ester, and converted to steroid hormones. • In the liver cholesterol is the precursor of the bile acids. • Low levels cholesterol might cause less flexibility of our blood vessel, low power to resist disease and… Cheng Xiaoli Zhengzhou University

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3.1.3 Membrane Protein The hydrophobic core is an impermeable barrier that prevents the diffusion of water-soluble solutes across the membrane. This simple barrier function is modulated by the presence of membrane proteins that mediate the transport of specific molecules, ions, and water across this otherwise impermeable bilayer.

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3.1.3 Membrane Protein The protein associated with a particular membrane are responsible for its distinctive activities. The complements and density of proteins associated with biomembranes vary acutely depending on cell type and subcellular location. The importance of membrane proteins is suggested from the finding that approximately 1/3 of all yeast genes encode membrane proteins. The relative abundance of genes for membrane proteins if even greater in multicellular organisms. Cheng Xiaoli Zhengzhou University

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Three forms proteins link to membrane : integral proteins (transmembrane proteins) , lipid-anchored membrane proteins and peripheral membrane proteins. Glycosylated integral protein

peripheral membrane protein with covalent lipid linker

transmembrane integral protein

Lopid-anchored membrane protein with Cheng Xiaoli Zhengzhou University

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Integral proteins or transmembrane proteins)

Some integral membrane proteins are transmembrane and make a single or multiple α-helical passes through the membrane. Integral protein can be marked off three different segment called domains: exoplasmic domain transmembrane domain Cytosolic domain Cheng Xiaoli Zhengzhou University

Integral proteins or transmembrane proteins) • The cytosolic and exoplasmic domain have hydrophilic

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exterior surfaces that interact with the aqueous solutions on the two faces of the membrane. • The membrane-spanning domain ( transmembrane domain ) form channels and pores, that allow move molecules in and out of cells exoplasmic domain transmembrane domain Cytosolic domain Cheng Xiaoli Zhengzhou University

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Integral proteins or transmembrane proteins)

•Glycophorin A always has its NH2 -terminal domain outside the red cell and its COOHterminal domain within the cytoplasm.

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Integral proteins or transmembrane proteins)

• The exoplasmic domain on the extracellular surface of the plasma membrane generally bind to other molecules, including external signaling proteins, ions, and small metabolites, and to adhesion molecules on other cells or in the external environment.

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Integral proteins or transmembrane proteins)

• The transmembrane domain lying along the cytosolic face of the plasma membrane have a wide range of functions, from anchoring cytoskeletal proteins to the membrane to triggering intracellular signaling pathways.

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Lipid-anchored membrane proteins

-NH2

outside lipid bilayer inside

-COOH

• Lipid-anchored membrane proteins are bound covalently linked to one or more lipid molecules. The polypeptide chain itself does not enter the bilayer. Cheng Xiaoli Zhengzhou University

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Peripheral membrane protein

• Peripheral protein do not interact with the hydrophobic core of the phospholipid bilayer. They just attach to the membrane surface by ionic interaction with an integral membrane protein or another peripheral membrane protein, or by interaction with the polar head groups of the phospholipids. • Peripheral protein are localized to either the cytosolic or the exoplasmic face Cheng Xiaoli Zhengzhou University of the plasma

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There are various subtypes of integral and peripheral membrane proteins.

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3.1.4 Membrane carbohydrate • The content of membrane carbohydrate in is 2-10 percent in membrane, and varies depend on the difference of cells. for example, there are proteins 52%, lipids 40% and carbohydrate 8% in the membrane of red cell. • Some carbohydrate combine with membrane lipid and form glucolipids via covalent bond, about 7% in red cell. The others combine with membrane proteins and form glucoproteins via covalent bond, about 93% in red cell.

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3.1.4 Membrane carbohydrate • It is important that all membrane carbohydrate pitch on the outside of plasmamembrane, but on the inside of the endomembrane system.

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3.1.4 Membrane carbohydrate • The function of membrane carbohydrate 1) Improve the stability of membranes. 2) Advance the fastness of to proteinase in extracellular matrix. 3) Help membrane proteins to form and maintain the correct packing and threedimensional configure. 4) Take part in the processes of cell signal recognition, cell adhension and cell junction 5) Give a correct position for transfer and orientation of new protein. 6) Lectin a class of glucoproteins, protect the cell and seed. 7) Some glucolipids are important blood group determinants. Cheng Xiaoli Zhengzhou University

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3.1.5 membranes fluidity

• Biological membranes are fluid, but that does not mean that every membrane macromolecule is mobile. • Phospholipids determine the fluidity of the membrane and are influenced by temperature, saturation of fatty acid chains and cholesterol.

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3.1.5 membranes fluidity Flip-flop (rarely occurs)

Rotation

Lateral diffusion (frequent)

• Phospholipids are able to move laterally across the membrane at very fast rates. • They are capable of transbilayer movement (flip-flop) in the endoplasmic reticulum, but flip-flop is a rare event in the plasma membrane. • They can rotate rapidly around a central axis.

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3.1.5 membranes fluidity

Integral membrane proteins can also rotate along their long axis within the membrane, but they do not flip-flop from one leaflet to the other. Several lines of evidence have indicated that membrane proteins are also capable of lateral movement within the plane of the membrane. Cheng Xiaoli Zhengzhou University

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membrane protein

0 minute

human cell

mouse cell

cell fusion

After 40 minute

Hybrid cell

Specific Fluorescent antibodies

Become mixed together

The use of cell fusion to reveal mobility Cheng Xiaoli Zhengzhou University of membrane proteins

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3.1.5 membranes fluidity

100

50

0 5

15

25

35

• The fluidity of membrane proteins is affected by temperature. The percentage of mosaic cells increases sharply as the temperature rises above 15℃, suggesting that the lipid undergoes a phase transition in that range from a gelating state to a fluid state Cheng Xiaoli Zhengzhou University

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Membrane phospholipids determine membrane transition temperature and how fluid membrane is at a certain temperature.

•The closer and more regular the packing of the hydrocarbon tails of the phospholipids, the more viscous and less fluid the membrane is. •The larger proportion of unsaturated hydrocarbon tails the membrane contains, the more fluid the membrane is (because each double bond in an unsaturated tail creates a small kink in the tail, which makes it more difficult for the tail to pack against one another) . •The more longer the fatty acid chain length of the tail, the more likely the hydrocarbon tails interact with one another, therefore decreasing the fluidityCheng of the Xiaoli Zhengzhou University

3.1.6. Membrane asymmetrically

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• It is important when thinking about membranes to keep in mind that a typical cell membrane tends to have a different composition on one side (inner leaflet ) than on the other (outer leaflet ). •Cell membranes are generally asymmetrical, presenting a very different face to the interior of the cell or organelle than to the exterior. The two halves of the bilayer often includes strikingly different selections of phospholipids and glycolipids. Moreover, the proteins are embedded in the bilayer with a specific orientation, which is crucial for their function. Cheng Xiaoli Zhengzhou University

3.1.6. Membrane asymmetrically 3.1.6.1 lipids

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asymmetry

Lipids in biological membranes are asymmetrically distributed across the bilayer; the amine-containing phospholipids are enriched on the cytoplasmic surface of the plasma membrane, while the choline-containing and sphingolipids are enriched on the outer surface. The maintenance of transbilayer lipid asymmetry is essential for normal membrane function, and disruption of this asymmetry is associated with cell activation or pathologic conditions. Cheng Xiaoli Zhengzhou University

3.1.6. Membrane asymmetrically 3.1.6.1 lipids

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asymmetry TPL 50 25

SM

exoplasmic

PC PE 20%

PS 10% 90%

25 80%

cytosolic

50

The asymmetric distribution of phospholipids in the plasma membrane of human RBC PE: phosphatidylethanolamine 磷脂酰乙醇胺 GL: glycolipid PS: phosphatidylserine 磷脂纤丝氨酸 PC: phosphatidylcholine 卵磷脂 SM: sphingomyelin 鞘磷脂 Cheng Xiaoli Zhengzhou University

3.1.6. Membrane asymmetrically 3.1.6.1 lipids

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asymmetry

PS is negatively charged of phospholipid kinds, that is why inner monolayer is negatively charged whereas external monolayer is positively charged. Therefore, the lipid bilayer can be considered as composed of two relatively stable, independent monolayers with different physical and chemical properties . Cheng Xiaoli Zhengzhou University

3.1.6. Membrane asymmetrically 3.1.6.1 lipids

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asymmetry

New phospholipid molecules

•The lipid asymmetry begins at the point of Phospholipid manufacture. New synthesis Lipid bilayer of ER Flippase adds to phospholipid catalyzes cytosolic half molecules are transfer of of the bilayer phospholipid synthesized by ERmolecules membrane-bound enzymes that use fatty acids available in the cytosolic monolayer and release the newly Symmetric growth of both halves of bilayer made phospholipid into the same monolayer. To enable the membrane as a whole to grow, a proportion of the lipid molecules then have to be transferred to the opposite monolayer. Cheng Xiaoli Zhengzhou University

3.1.6. Membrane asymmetrically 3.1.6.1 lipids

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asymmetry

This transfer is catalyzed by enzymes called flippase. It has been suggested that the flippases may transfer specific phospholipid molecules selectively, so that different types become concentrated in the two halves of the monolayer. Cheng Xiaoli Zhengzhou University

3.1.6. Membrane asymmetrically 3.1.6.1 lipids

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asymmetry

Loss of Membrane Asymmetry Loss of membrane asymmetry (phosphatidylserine redistribution) is a very early event in Apoptosis. Anti-Phosphatidylserine is used to detect the flip. Cheng Xiaoli Zhengzhou University

3.1.6. Membrane 3.1.6.2 portions asymmetrically

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asymmetry

1. many different kinds of proteins are in the cell membranes a. each type has a unique conformation and orientation b. flip flop of proteins does not occur, so their asymmetry is absolute c. conformational changes of protein can occur 2. carbohydrates of glycoproteins always at outer surface Cheng Xiaoli Zhengzhou University

3.1.6. Membrane asymmetrically 3.1.6.3 sugar residues

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asymmetry

•The sugar residues are always found on the noncytoplasmic side of the membrane.

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3.1.7 Modals of cell Membrane It is upon the works of Danielli and Davson’s "sandwich type" Membrane modal, Robertson’s Unit Membrane Model, and the others scientific achievements that Singer and Nicholson proposed the fluid mosaic model of membranes In 1972, stating that the membrane proteins are globular and to float within the lipid bilayer.

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3.1.7 Modals of cell Membrane

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• The Fluid Mosaic Model

The globular membrane proteins are embedded within the bilayer, with hydrophobic portions of the proteins buried within the hydrophobic core of the lipid bilayer, and hydrophilic portions of the proteins exposed to the aqueous environment, and the proteins float within the lipid bilayer. Cheng Xiaoli Zhengzhou University

3.2 Modals of cell Membrane The fluid mosaic model was modified many

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times later because of more recent discoveries, but it still remains the model preferred by biologists today. It explains the current knowledge of membrane structure and also serves as the basis for our understanding of how membranes function.

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3.2 Common functions of plasma membrane 1. Plasma membranes act as a permeability barrier that prevents the entry of unwanted materials from the extracellular milieu and the exit of needed metabolites. 2. In animal cells specialized areas of the plasma contain proteins and glycolipids that form specific junctions between cells to strengthen tissues and to allow the exchange of metabolites 3. Certain plasma membrane proteins anchor cells to components of the extracellular matrix. Cheng Xiaoli Zhengzhou University

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3.2 Common functions of plasma membrane 4. Certain plasma membrane contain receptor proteins that bind specific signaling molecules(e.g., hormones, growth factors, neurotransmitters), leading to various cellular responses. 5. Plasma membrane take part in the compartmentalization of cell. ... and many others functions of the plasma membrane in bacterial, fungal, and plant etc. Cheng Xiaoli Zhengzhou University

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Summar y

1. The plasma membrane is a selectively permeable barrier found on the surface of 2. The basic structure of biological membranes cells. is a lipid bilayer. 3. There are three basic types of membrane proteins: integral proteins (transmembrane proteins) , lipid-anchored membrane proteins and peripheral membrane proteins. 4. Proteins, sugar residues and lipids are asymmetrically distributed across membranes. 5. Biological membranes are fluid. Cheng Xiaoli Zhengzhou University

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QUESTION S Variation in Phospholipid 1. What is the Effects of

Fatty Acid Composition ? 2. What are the functions of membrane carbohydrate ? 3. Please explain the statement: plasma membrane is asymmetrical membrane. 4. What is the Fluid Mosaic Model ? 5. What factors affect the degree of membrane fluidity ? 6. What are Common functions of plasma membrane in cells ?

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