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Page 1: Cell membrane bch405 mic_3

Cell Membranes

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Structure of Cell Membrane

Structure and function of cell are critically dependent on membrane

• Separates interior of cell from outside

• Define internal compartments

Formation of biological membrane depend on

• Properties of lipids

• All biological membranes share a common structural organization

Bilayer of lipids with associated proteins

Cell Membrane

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Membrane structure

Phopholipids are major structural component of membranes

consisting of two hydrophobic fatty acid chain linked to

phosphate joined to polar head groups

Cell Membrane 3

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Lipid constitute approximately 50% of mass of cell membrane, composition of cell membranes varies with type of membrane

e.g

• inner membrane of mitochondria (75%) of proteins

• Plasma membrane 50% lipid & 50% proteins

• Plasma membrane of Ecoli consist of phosphotidylethanolamine which constitutes 80% of total lipids

Mammalian plasma membranes are complex containing four different phospholipids Phosphotidylcholine

Phosphotidyl ethanolamine

Phosphotidyl serine

Sphingomylein

Glycolipids and cholestrol 40% of total membrane lipids

50-60% of total membrane lipids

Cell Membrane 4

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Contd….

An important property of lipid bilayer is that they behave as two dimensional fluids

◦ Lipids and proteins are free to rotate & move in lateral directions

Fluidity of lipid bilayer is determined by

◦ Lipid composition

◦ Temperature

Interaction between shorter fatty acid chains are weaker than those with longer chains

Membranes containing shorter fatty acid chains

◦ Less rigid and remain fluid at < temperature

Membrane fluidity is also increased by

◦ Unsaturated fatty acids

Cell Membrane

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cholesterol plays a distinct role in determining membrane fluidity because of its hydrocarbon ring structure

The rigid hydrocarbon rings of cholesterol therefore interact with the regions of the fatty acid chains that are adjacent to the phospholipid head groups

This interaction decreases the mobility of the outer portions of the fatty acid chains, making this part of the membrane more rigid.

On the other hand, insertion of cholesterol interferes with interactions between fatty acid chains, thereby maintaining membrane fluidity at lower temperatures

Cell Membrane

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Membrane proteins

Proteins constitute approximately 25-75%

of mass of membranes

Fluid Mosaic Model In 1972, S.J. Singer & G.

Nicolson proposed that

membrane proteins are

inserted into the

phospholipid bilayer

Cell Membrane

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Contd….

Phospholipids provide basic structural organization of membrane

Membrane proteins carry out specific functions of membranes

Proteins divided into two broad classes based on

nature of their association with cell membrane

• Integral membrane Proteins

• Peripheral membrane proteins

Cell Membrane

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Like phospholipids transmembrane proteins (intergral) are amphipathic molecules with their hydrophilic portions exposed to extracellular enviroment on both sides of membrane

Within membrane ◦ nonpolar amino acids hydrophobic

anchors protein into membrane

On outer surfaces of membrane

◦ polar amino acids hydrophilic

extend into extracellular fluid & into cytosol

Cell Membrane

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Contd…

Proteins can also be anchored in membranes by lipids that are

covalently attached to the polypeptide chain

Distinct lipid modifications anchor proteins to the cytosolic and

extracellular faces of the plasma membrane

Proteins can be anchored to cytosolic face of plasma membrane by

addition of

14 carbon fatty acid (myristic acid)

16 carbon fatty acid (palmitic acid)

15-20 carbon prenyl groups to side chains of cysteine residues

Alternatively, proteins are anchored to the extracellular face of the

plasma membrane by the addition of glycolipids to their carboxy

terminus.

Cell Membrane

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The Glycocalyx

The surface of cell is covered by carbohydrate

coat known as glycocalyx formed of Oligosaccharides of glycolipids

Transmembrane glycoproteins

• Functions • Protect cell surface from ionic and mechanical stress

• Barriers to invading microrganism

• Oligosaccharides of glycocalyx participate in cell-cell

interactions

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Cell Membrane

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A well studied example of physiological

interaction involving the glycocalyx involves

• Adhesion of white blood cells (leukocytes) to

endothelial cells that line the blood vessels

Allows leukocytes to leave the circulatory

system and mediate inflammatary response in

injured tissues

Initial step in interaction is mediated by

◦ Selectins (transmembrane protein) Recognizes carbohydrate on cell surface

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Cell Membrane

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• Two members of selectin family E-selectins

P-selectins

• L-selectin is expressed by leukocytes and recognizes an

oligosaccharide on surface of endothelial cells

• Oligosacchride exposed on cell surface thus provide a

set of markers that help identify distinct cell types

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Expressed by endothelial cells and

platelets bind to oligosaccharides on

surface of leukocytes

Cell Membrane

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Functions of Cell Membrane

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Functions of Cell Membrane

1. Selective permeability Enables cells to control and maintain its internal

composition

Small uncharged molecules diffuse through membrane

Bilayer is impermeable to • large polar molecules

• charged molecules such as ions

Many such molecules are able to cross lipid bilayer via the action of specific transmembrane proteins (transporters) which determines ◦ Selective permability of membranes

Transmembrane proteins contain multiple membrane spaning regions

Functions of cell membrane

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Functions of cell membrane

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There are two general classes of membrane transport proteins

Channel proteins:

Form open pores allowing passage of any small molecule by free diffusion

◦ e.g : Na, K, Ca, Cl

Pores are not permanently open rather they can be selectively opened or closed in response to

Extracellular signals

◦ Such channels are extensively studied in Muscle & nerve cells

Response to extracellular signals

Functions of cell membrane 20

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Carrier proteins

• Selectively bind and transport small molecules

such as glucose

• Carrier proteins act like enzymes facilitate the

passage of small molecules across membrane

◦ Carrier proteins bind specific molecules

◦ Undergo conformational change that open

channel

Functions of cell membrane

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Functions of cell membrane 22

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Mechanism of Transport

Passive transport

Molecules transported by either proteins cross the

membrane in energetically favorable direction

• Determined by concentration

• Electrochemical gradient

Active Transport:

Molecules can be transported in energetically

unfavorable direction if their transport in that

direction is coupled with ATP hydrolysis

Functions of cell membrane

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Functions of cell membrane 24

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Types of membrane proteins

In addition to transport membrane proteins have diversified roles in cell

• Cell-cell recognition proteins

• Integrins

• Intercellular junction proteins

• Signal transduction proteins

Functions of cell membrane

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Cell-cell recognition proteins - identify

type of cell and identify a cell as “self”

versus foreign

• Most are glycoproteins

Carbohydrate chains vary between species,

individuals, and even between cell types in a given

individual.

Glycolipids also play a role in cell recognition

Functions of cell membrane

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Contd…

Integrins are a type of integral protein

• The cytoskeleton attaches to integrins on the

cytoplasmic side of the membrane

• Integrins strengthen the membrane

Intercellular junction proteins - help like

cells stick together to form tissues

Functions of cell membrane

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Enzymatic proteins. Many enzymes are embedded in membranes, which

attract reacting molecules to the membrane surface.

Enzymes needed for metabolic pathways can be aligned

adjacent to each other to act like an assembly line for

the reactions.

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