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Ref: MBoC (5th Edition), Alberts • Johnson • Lewis • Raff • Roberts • Walter Chapter 10 Membrane Structure

Lecture 1 Introduction and Membrane

Hualin Zhong 01/30/2012

•  Cells arise only from preexisting cells.

•  Every cell has genetic information whose expression enables it to produce all its components.

2 Cell, Lewin et al. 2006

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Cell, Lewin et al. 2006

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A Prokaryotic Cell Consists of a Single Compartment •  The plasma membrane of a prokaryote surrounds a single

compartment.

•  The entire compartment has the same aqueous environment. •  Genetic material occupies a compact area within the cell. •  The plasma membrane is surrounded by a cell wall.

Cell, Lewin et al. 2006

5 Figure 1-30 Molecular Biology of the Cell, Fifth Edition (© Garland Science 2008)

The Major Features of Eukaryotic Cell

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Membranes Allow the Cytoplasm to Maintain Compartments with Distinct Environments

Organelles that are surrounded by membranes can maintain internal environments that are different from the surrounding cytosol.

Cell, Lewin et al. 2006

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Figure 10-1

Three Views of a Cell Membrane

A.  A cross section EM of a plasma membrane (human red blood cell). B.  A drawing of 2-D view of a cell membrane. C.  A drawing of 3-D view of a cell membrane.

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Lipids

•  Lipids are water-insoluble biomolecules that are highly soluble in organic solvents, such as chloroform.

•  Biological roles of lipids: - serve as fuel molecules. - signal molecules and messages in signal transduction pathways. - major components of membranes.

•  Membrane lipids are amphipathic molecules containing a hydrophilic and a hydrophobic moiety. Three common types of membrane lipids are:

- Phospholipids (major class) - Glycolipids - Cholesterol

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The Parts of a Phosphoglyceride Molecule

Figure 10-2

phosphatidylcholine

scheme formula space-filling model

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Sphingomyelin (D) is derived from sphingosine (E) and is therefore a sphingolipid. Only phosphatidylserine carries a net negative charge; the other three are electrically neutral at physiological pH, carrying one positive and one negative charge.

Four Major Phospholipids in Mammalian Plasma

Figure 10-3

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Figure 10-4

* In addition to phospholipids, the lipid bilayers in many cell membranes contain cholesterol and glycolipids. Eukaryotic plasma membranes contain especially large amounts of cholesterol—up to one molecule for every phospholipid molecule.

Figure 10-5 Cholesterol in a lipid bilayer.

The Structure of Cholesterol

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(A) Acetone readily dissolves in water, because acetone is polar, it can form favorable electrostatic interactions with water molecules, which are also polar. (B) 2-methyl propane is virtually insoluble in water, because it is entirely hydrophobic, it cannot form favorable interactions with water, it would force adjacent water molecules to reorganize into icelike cage structures, which increases the free energy.

How Hydrophilic and Hydrophobic Molecules Interact Differently with Water

Figure 10-6

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Figure 10-7

Figure 10-8

Packing arrangements of lipid molecules in an aqueous environment.

A phospholipid bilayer spontaneously closes to form a sealed compartment.

Stable

Unstable

Membrane Lipids Are Amphipathic Molecules

* Most membrane lipids spontaneously form bilayers.

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Liposomes-Lipid vesicles

Figure 10-9 An EM of unfixed, unstained phospholipid vesicles (called liposomes) in water rapidly frozen to liquid nitrogen temperature.

A drawing of a small spherical liposome seen in cross section.

Liposomes are commonly used as model membranes in experimental studies.

A schematic diagram of a liposome containing a hydrophilic polymer (such as polyethylene glycol) to protect it from destruction by immune cells, antibody molecules that target it to specific body tissues, a water-soluble drug enclosed in the fluid-filled interior chamber, and a lipid-soluble drug in the bilayer.

A Schematic Diagram of a Liposome

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(A)  A model of the lipid bilayer accounts for almost all of the measurable properties of a synthetic lipid bilayer, such as its thickness, number of lipid molecules per membrane area, depth of water penetration, and unevenness of the two surfaces. Note that the tails in one monolayer can interact with those in the other monolayer, if the tails are long enough.

(B) The different motions of a lipid molecule in a bilayer.

The Mobility of Phospholipid Molecules in an Artificial Lipid Bilayer

* A lipid bilayer can be considered as a two-dimensional fluid.

Figure 10-11

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Figure 12-58

The Role of Phospholipid Translocators in Lipid Bilayer Synthesis

1) new lipid molecules are added only to the cytosolic half of the bilayer

2) lipid molecules do not flip spontaneously from one monolayer to the other,

a membrane-bound phospholipid translocator (called a scramblase) is required to transfer lipid molecules from the cytosolic half to the lumenal half so that the membrane grows as a bilayer. The scramblase is not specific for particular phospholipid head groups and therefore equilibrates the different phospholipids between the two monolayers.

(B) Fueled by ATP hydrolysis, a head-group-specific flippase in the

plasma membrane actively flips phosphatidylserine and phosphatidyl-ethanolamine directionally from the extracellular to the cytosolic leaflet, creating the characteristically

asymmetric lipid bilayer of the plasma membrane of animal

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1.  The double bonds make it more difficult to pack the chains together, thereby making the lipid bilayer more difficult to freeze.

2.  Because the hydrocarbon chains of unsaturated lipids are more spread apart, lipid bilayers containing them are thinner than bilayers formed exclusively from saturated lipids.

The Influence of Cis-Double Bonds in Hydrocarbon Chains

Figure 10-12

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Cis-Double Bonds in Hydrocarbon Chains Influence the Packing of Fatty Acids Chains in a Membrane

Stearate (C18) Stearate (C18) +!oleate (C18- cis-∆9)!

Chain length and degree of unsaturation of fatty acids affect the melting temperature of the lipid bilayer.

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Lateral phase separation in artifical lipid bilayers. (A) Giant liposomes produced from a 1:1 mixture of phosphatidylcholine and

spingomyelin form uniform bilayers. (B)  Liposomes produced from a 1:1:1 mixture of phosphatidylcholine, spingomyelin, and

cholesterol form bilayers with two immiscible phases. The liposomes are stained with trace concentrations of a fluorescent dye that preferentially partitions into one of the phases.

Despite Their Fluidity, Lipid Bilayers Can Form Domains of Different Compositions

* The van der Waals attractive forces between neighboring hydrocarbon tails are not selective enough to hold groups of phospholipid molecules together. With certain lipid mixtures, however, different lipids can come together transiently, creating a dynamic patchwork of different domains.

Figure 10-13

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(A)  The surface contours of a synthetic bilayer containing lipid rafts, analyzed by atomic force microscopy. The raft areas, shown in orange, are thicker than the rest of the bilayer (the rafts primarily contain sphingomyelin and cholesterol). The sharp, yellow spikes are incorporated protein molecules, which are attached to the bilayer by a glycosylphosphatidyl-inositol (GPI) anchor, and preferentially partition into the raft domains.

(B) Because of both their increased thickness and lipid composition, rafts are thought to concentrate specific membrane proteins (dark green).

The Effects of Lipid Rafts in Artificial Lipid Bilayers

(A) (B)

Figure 10-14

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Four Major Phospholipids in Mammalian Plasma and Cholesterol

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Neutral lipids are deposited between the two monolayers of the endoplasmic reticulum membrane. There, they aggregate into a 3D lipid droplet, which buds and pinches off from the ER membrane as a unique organelle, surrounded by a single monolayer of phospholipids and associated proteins.

A Model for the Formation of Lipid Droplets

Figure 10-15

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Figure 10-16 The colors used for the phospholipid head groups are those introduced in Figure 10–3. In addition, glycolipids are drawn with hexagonal polar head groups (blue). Cholesterol (not shown) is thought to be distributed roughly equally in both monolayers.

The Asymmetrical Distribution of Phospholipids and Glycolipids in the Lipid Bilayer of Human Red Blood Cells

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(A)  Some extracellular signals activate phosphoinositide (PI) 3-kinase, which phosphorylates inositol phospholipids, creating docking sites for various intracellular signaling proteins.

(B) Some extracellular signals activate phospholipases that cleave inositol phospholipids, generating fragments that help relay the signal into the cell.

(C) The sites where different classes of phospholipases cleave phospholipids [phosphatidylinositol (4,5) diphosphate].

(A) (B)

(C)

Two signaling functions of inositol phospholipids in the cytosolic monolayer of the plasma membrane:

The Asymmetry of the Lipid Bilayer Is Functionally Important

Figure 10-17