MEMBRANES

2

Membranes function to organize biological processes by

compartmentalizing them. Indeed, the cell, the basic unit of

life, is essentially defined by its enveloping plasma membrane.

3

Moreover, in eukaryotes, many subcellular organelles,

such as nuclei, mitochondria, chloroplasts, the endoplasmic

reticulum, and the Golgi apparatus are likewise

membrane bounded.

4

FUNCTIONS OF MEMBRANE

4

Protective barrier

Regulate transport in & out of cell (selectively permeable)

Allow cell recognition

Provide anchoring sites for filaments of cytoskeleton

5

Provide a binding site for enzymes

Interlocking surfaces bind cells together (junctions)

Contains the cytoplasm (fluid in cell)

6

Membrane Structure and Function

Membrane Structure

Lipids and proteins are the main components of the membranes, although carbohydrates are also important.

7

The most abundant lipids in most membranes are phospholipids

Phospholipids and most of proteins of membrane are amphipathic molecules.

8

Amphipathic molecules : A molecule that has both hydrophilic region and a hydrophilic regions.

.

HISTORY OF MEMBRANE STUDIES

11

The molecules in the bilayer are arranged such that the hydrophobic fatty acid tails are sheltered from water

while the hydrophilic

phosphate groups

interact with water.

14

Further investigation revealed two problems.First, not all membranes were alike, but

differed in thickness, appearance when stained, and percentage of proteins to lipids.

15

Second, measurements showed that membrane proteins are actually not very soluble in water.• Membrane proteins are amphipathic, with

hydrophobic and hydrophilic regions.• If at the surface, the hydrophobic regions

would be in contact with water.

17

THE FLUID MOSAIC MODEL

1818

Unit membrane model

1919

Cell membrane and its surface structure

LIPID RAFTS MODEL

20

PROTEIN, LIPID AND CARBOHYDRATE COMPOSITIONS OF SOME MEMBRANES

21

Depending on the precise conditions and the nature

of the lipids, three types of lipid aggregates can form

when amphipathic lipids are mixed with water

22

• a) Micelle

• (b) Bilayer

• (c) Liposome

23

MICELLES

Micelles are spherical structures that contain

anywhere from a few dozen to a few thousand amphipathic

molecules. Their hydrophobic regions aggregated in the interior,

where water is excluded, and their hydrophilic head

groups at the surface, in contact with water.

24

BILAYER

in which two lipid monolayers (leaflets) form

a two-dimensional sheet. Bilayer formation occurs most

readily when the cross-sectional areas of the head group

and acyl side chain(s) are similar

25

The hydrophobic portions

in each monolayer, excluded from water, interact with

each other. The hydrophilic head groups interact with

water at each surface of the bilayer.

26

LIPOSOME

the bilayer sheet is relatively

unstable and spontaneously forms a third type of

aggregate: it folds back on itself to form a hollow sphere,

a vesicle or liposome.

27

By forming vesicles,

bilayers lose their hydrophobic edge regions, achieving

maximal stability in their aqueous environment. These

bilayer vesicles enclose water, creating a separate aqueous

compartment.

28

BIOLOGICAL MEMBRANES

Biological membranes are composed of proteins associated with a lipid bilayer matrix. Their lipid fractions consist of complex mixtures that vary according to the membrane

source and, to some extent, with the diet and

environment of the organism that produced the membrane

29

.

Membrane proteins carry out the dynamic processes

associated with membranes, and therefore specific proteins

occur only in particular membranes.

30

MEMBRANE STRUCTURE AND COMPOSITION

MEMBRANE IS A COLLAGE OF PROTEINS & OTHER MOLECULES EMBEDDED IN THE FLUID MATRIX OF THE LIPID BILAYER

Extracellular fluid

Cholesterol

Cytoplasm

Glycolipid

Transmembraneproteins

Filaments ofcytoskeleton

Peripheralprotein

Glycoprotein

Phospholipids

32

PHOSPHOLIPIDS• Fatty acid tails

• hydrophobic

• Phosphate group head

• hydrophilic

• Arranged as a bilayer

Fatty acid

Phosphate

33

PHOSPHOLIPID BILAYER

polarhydrophilicheads

nonpolarhydrophobictails

polarhydrophilicheads

34

MORE THAN LIPIDS… • In 1972, S.J. Singer & G. Nicolson proposed that membrane

proteins are inserted into the phospholipid bilayer

It’s like a fluid…It’s like a mosaic…It’s the Fluid Mosaic Model!

35

MEMBRANE FAT COMPOSITION VARIES• Fat composition affects flexibility

• membrane must be fluid & flexible

• about as fluid as thick salad oil

36

MEMBRANE PROTEINS• Proteins determine membrane’s specific functions

• cell membrane & organelle membranes each have unique collections of proteins

37

PERIPHERAL PROTEINS

•loosely bound to surface of membrane•cell surface identity marker (antigens)

38

• INTEGRAL PROTEINS • penetrate lipid bilayer, usually across

whole membrane

• transmembrane protein

• transport proteins• channels, permeases (pumps)

39

Integral protein(hydrophobic domaincoated with detergent)

Peripheral protein

40

PROTEINS DOMAINS ANCHOR MOLECULE

• Within membrane• nonpolar amino acids • hydrophobic • anchors protein

into membrane

Polar areasof protein

Nonpolar areas of protein

41

• On outer surfaces of membrane• polar amino acids • hydrophilic• extend into extracellular fluid & into

cytosol

42

NH2

H+

COOH

Cytoplasm

Retinalchromophore

Nonpolar(hydrophobic)a-helices in thecell membrane H+

Porin monomer

b-pleated sheets

Bacterialoutermembrane

proton pump channel in photosynthetic bacteria

water channel in bacteria

function through conformational change = shape change

function through conformational change = shape change

EXAMPLES

43

MANY FUNCTIONS OF MEMBRANE PROTEINS

Outside

Plasmamembrane

InsideTransporter Cell surface

receptorEnzymeactivity

Cell surface identity marker

Attachment to thecytoskeleton

Cell adhesion

44

MEMBRANE CARBOHYDRATES

• Play a key role in cell-cell recognition

• ability of a cell to distinguish one cell from another

• antigens

• important in organ & tissue development

• basis for rejection of foreign cells by immune system

45

Any Questions??

2007-2008

MOVEMENT ACROSS THE CELL MEMBRANE

47

DIFFUSION• 2nd Law of Thermodynamics

governs biological systems

• universe tends towards disorder (entropy)

Diffusion movement from high low concentration

Diffusion movement from high low concentration

48

DIFFUSION• Move from HIGH to LOW concentration

• “passive transport”

• no energy needed

diffusion osmosis

movement of water

49

DIFFUSION ACROSS CELL MEMBRANE• Cell membrane is the boundary between inside &

outside…

• separates cell from its environment

INfoodcarbohydratessugars, proteinsamino acidslipidssalts, O2, H2O

OUTwasteammoniasaltsCO2

H2O products

cell needs materials in & products or waste out

IN

OUT

Can it be an impenetrable boundary? NO!

50

DIFFUSION THROUGH PHOSPHOLIPID BILAYER• What molecules can get through directly?• fats & other lipids

inside cell

outside cell

lipid

salt

aa H2Osugar

NH3

What molecules can NOT get through directly?

polar molecules H2O

ions salts, ammonia

large molecules starches, proteins

51

CHANNELS THROUGH CELL MEMBRANE• Membrane becomes semi-permeable with protein

channels

• specific channels allow specific material across cell membrane

inside cell

outside cell

sugaraaH2O

saltNH3

52

FACILITATED DIFFUSION• Diffusion through protein channels• channels move specific molecules across

cell membrane

• no energy needed

“The Bouncer”“The Bouncer”

open channel = fast transport

facilitated = with help

high

low

53

ACTIVE TRANSPORT• Cells may need to move molecules against concentration

gradient• shape change transports solute from

one side of membrane to other • protein “pump”• “costs” energy = ATP

“The Doorman”“The Doorman”

conformational change

ATP

low

high

54symportantiport

ACTIVE TRANSPORT

ATP ATP

55

TRANSPORT SUMMARYsimplediffusion

facilitateddiffusion

activetransport

ATP

56

HOW ABOUT LARGE MOLECULES?• Moving large molecules into & out of cell

• through vesicles & vacuoles

• endocytosis

• phagocytosis = “cellular eating”

• pinocytosis = “cellular drinking”

• exocytosis

exocytosis

57

ENDOCYTOSIS

phagocytosis

pinocytosis

receptor-mediated endocytosis

fuse with lysosome for digestion

non-specificprocess

triggered bymolecular signal

2007-2008

THE SPECIAL CASE OF WATER

MOVEMENT OF WATER ACROSS THE CELL MEMBRANE

59

• Diffusion of water from high concentration of water to low concentration of water

• across a semi-permeable membrane

60

CONCENTRATION OF WATER• Direction of osmosis is determined by comparing total

solute concentrations

• Hypertonic - more solute, less water

• Hypotonic - less solute, more water

• Isotonic - equal solute, equal water

hypotonic hypertonic

water

net movement of water

61freshwater balanced saltwater

MANAGING WATER BALANCE• Cell survival depends on balancing water uptake & loss

62

AQUAPORINS• Water moves rapidly into & out of cells

• evidence that there were water channels

1991 | 2003

Peter AgreJohn Hopkins

Roderick MacKinnonRockefeller

63

Any Questions??

64

Endocytosis / Exocytosis (Endocytosis / Exocytosis.EXE)

65

Sodium-Potassium Pump (Sodium-Potassium Pump.EXE)

SUMMARY

68

THE COMPOSITION AND ARCHITECTUREOF MEMBRANES

69

Biological membranes define cellular boundaries,

divide cells into discrete compartments, organize

complex reaction sequences, and act in signal

reception and energy transformations.

70

Membranes are composed of lipids and proteinsin varying combinations particular to eachspecies, cell type, and organelle. The fluidmosaic model describes features common to allbiological membranes. The lipid bilayer is thebasic structural unit.

71

Fatty acyl chains of phospholipids and the steroid nucleus of sterols are oriented toward the interior of the bilayer;their hydrophobic interactions stabilize thebilayer but give it flexibility.

72

Peripheral proteins are loosely associated withthe membrane through electrostatic interactionsand hydrogen bonds or by covalently attachedlipid anchors..

73

Integral proteins associate firmlywith membranes by hydrophobic interactionsbetween the lipid bilayer and their nonpolaramino acid side chains, which are orientedtoward the outside of the protein molecule

74

75

76

Membrane Dynamics

77

Lipids in a biological membrane can exist inliquid-ordered or liquid-disordered states; inthe latter state, thermal motion of acyl chainsmakes the interior of the bilayer fluid. Fluidityis affected by temperature, fatty acidcomposition, and sterol content.

78

Flip-flop diffusion of lipids between the innerand outer leaflets of a membrane is very slowexcept when specifically catalyzed by flippases.

79

Lipids and proteins can diffuse laterally withinthe plane of the membrane, but this mobility islimited by interactions of membrane proteinswith internal cytoskeletal structures andinteractions of lipids with lipid rafts.

80

One classof lipid rafts consists of sphingolipids andcholesterol with a subset of membrane proteinsthat are GPI-linked or attached to severallong-chain fatty acyl moieties.

81

Caveolin is an integral membrane protein thatassociates with the inner leaflet of the plasmamembrane, forcing it to curve inward to formcaveolae, probably involved in membranetransport and signaling.

82

Integrins are transmembrane proteins of theplasma membrane that act both to attach cells to each other and to carry messages betweenthe extracellular matrix and the cytoplasm.

■ Specific proteins mediate the fusion of twomembranes, which accompanies processes suchas viral invasion and endocytosis andexocytosis.

83

SOLUTE TRANSPORT ACROSSMEMBRANES

Movement of polar compounds and ions across

biological membranes requires protein

transporters. Some transporters simply

facilitate passive diffusion across the membrane

from the side with higher concentration to the

side with lower.

84

Others bring about active

movement of solutes against an electrochemical

gradient; such transport must be coupled to a

source of metabolic energy.

85

Carriers, like enzymes, show saturation andstereospecificity for their substrates. Transport via these systems may be passive or active.■

86

Primary active transport is driven by ATP orelectron-transfer reactions; secondary activetransport, by coupled flow of two solutes, one of which (often H or Na) flows down itselectrochemical gradient as the other is pulled up its gradient.

87

The GLUT transporters, such as GLUT1 oferythrocytes, carry glucose into cells byfacilitated diffusion. These transporters areuniporters, carrying only one substrate.

88

Symporters permit simultaneous passage of two substances in the same direction; examples arethe lactose transporter of E. coli, driven by theenergy of a proton gradient (lactose-Hsymport), and the glucose transporter ofintestinal epithelial cells, driven by a Nagradient (glucose-Na symport)

89

Antiporters mediate simultaneous passage of two

substances in opposite directions; examples are

the chloride-bicarbonate exchanger of

erythrocytes and the ubiquitous NaK

ATPase.

90

THANK YOU