2nd Edition 1

Chapter 2:

Cell membrane

cell surface

and

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Outline

2.1 Components and structure of cell membrane

2.2 Transmembrane transport

2.3 Cell adhesion molecules and cell junction

2.4 Extracellular matrix and cell wall

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2.1 Components and structure of cell membrane

• All cells are surrounded by a layer of membrane;

• In eukaryote cell, membrane compartmentalizes the

cell into sub-compartments termed organelles;

• Prokaryote cell lacks sub-compartment.

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eukaryote and prokaryote cell(See Chapter 1)

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Common functions of plasma membrane

Act as permeability barrier

Intimately engaged in the assembly of cell walls

Form specific junctions between cells

Anchor components of the extracellular matrix

Contain receptor proteins that bind specific signaling

molecules

Take part in the compartmentalization of cell

Energy transduction

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The structure of plasma membrane

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Basic compositions

lipids

proteins

saccharide

2.1 Components and structure of cell membrane

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The basic compositions of some bio-membranes

Membrane Proteins (%) Lipids (%) Saccharide (%)

Plasma membrane

Red blood cell 49 43 8

Myelin membrane 18 79 3

Liver cell 54 36 10

Nucleus membrane 66 32 2

Golgi body 64 26 10

Endoplasmic reticulum 62 27 10

Mitochondrion

Outside membrane 55 45 trace

Inside membrane 78 22 -

Chloroplast 70 30 -

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2.1.1 Lipids in biomembrane

main types of membrane lipids:

Phospholipid

• Phosphoglycerides

• Sphingolipids

Cholesterol (steroids)

amphipathic molecules

hydrophilic head group + hydrophobic tail group

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Phosphoglycerides

PC: phosphatidylcholine X=cholinePE: phosphatidylethanolamine X=ethanolaminePS: phosphatidylserine X=serine

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phosphatidylcholine

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The class of sphingolipids

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Sphingomyelin

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Structure of major phospholipid molecules

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Structure of glycolipid molecules in plasma membrane

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Cholesterol

Cholesterol is smaller than the other lipids of the

membrane and less amphipathic.

Cholesterol is absent from the plasma membranes

of most plant.

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2.1.2 Proteins in biomembrane

Three forms of proteins link to membrane

• Integral proteins (Transmembrane proteins)

• Lipid-anchored membrane proteins

• Peripheral membrane proteins

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Proteins associated with the lipid bilayer

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proteins on cell membrane can be classed to :

• Channel proteins: to form pores for the free transport of small

molecules and ions across the membrane;

• Carrier proteins: to facilitated diffusion and active transport of

molecules and ions across the membrane;

• Cell recognition proteins: to identifie a particular cell;

• Receptor proteins: to bind specific molecules, such as hormones

and cytokines, and mediate signal transduction;

• Enzymatic proteins: that catalyze specific chemical reactions.

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Integral proteins

Cytosolic domain

Exoplasmic domain

Transmembrane

domain

hydrophilic surfaces studded in membrane

interact with the aqueous solutions

interact with the hydrocarbon core of the phospholipid bilayer

bind to other molecules or ions

anchoring cytoskeletal proteins

triggering intracellular signaling pathways

form channels and pores

glycosylated

localized to the exoplasmic domains

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Structural basis of integral proteins

(A) α-helix model of bacteriorhodopsin

(B): -barrel model of one subunit of OmpX

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Lipid-anchored membrane proteins

covalent bound to

lipid molecules of

the phospholipid

bilayer.

polypeptide chain

does not enter the

phospholipid bilayer.

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Peripheral membrane proteins

bound to the membrane indirectly by interactions

with integral membrane proteins or directly by

interactions with lipid head groups.

localized to either the cytosolic or the exoplasmic

face of the plasma membrane.

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2.1.3 Membrane carbohydrate

• 2%~10% of membrane content depending on

cell types;

• covalently bound to membrane proteins and

lipids to form glycoproteins or glycolipids;

• all membrane carbohydrate pitch on the

outside of plasma membrane.

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Structure of glycolipid molecules in plasma membrane

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Function of membrane carbohydrate

• Protect cells against mechanical and chemical

damage;

• Preventing unwanted protein-protein interactions;

• Help membrane proteins to form correct three-

dimensional configures ;

• Help to transfer of new proteins to correct position;

• Cell recognition, cell adhension and cell junction.

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2.1.4 structure characters of plasma membrane

Fluid mosaic model

Lipid raft model

Membrane fluidity

Membrane asymmetry

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Arrangement of lipid molecules in an aqueous environment

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Fluid mosaic model

S.J. Singer and G.L. Nicolson in1972

•membranes as dynamic structures in which lipids and proteins are mobile

•lipid bilayers form the basis of the membranes

•proteins either span the bilayer or are attached to either side of the lipid membrane;

•the membranes are asymmetrical

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Lipid rafts model

a complementation for the fluid mosaic model

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Membrane fluidity

The possible movements of phospholipids in a membrane

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The physical state of the lipid of a membrane

• phase transition

liquid-like state frozen crystalline gel

• transition temperature:

the temperature point when the lipid phase

transition appears.

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Factors influence bilayer fluidity

• unsaturation state of the fatty acids in the bilayer;

• the length of the hydrocarbon chains of a lipid;

• cholesterol molecules:

Decrease bilayer fluidity

above the transition

temperature

increase bilayer fluidity

below transition temperature

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Membrane fluidity

Cell fusion technique reveals membrane protein mobility

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Membrane fluidity

Membrane protein mobility revealed by FRAP technique

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Factors influence membrane protein mobility

• Integral proteins

• Membrane lipid fluidity

• ECM

• Cell junctions

• Ligand, antibody and

drug molecules

Restriction on membrane protein mobility by ECM

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Membrane Asymmetry

• The two halves of the bilayer often contain different types of

phospholipids and glycolipids.

• The proteins embedded in the bilayer have a specific orientation

Freeze-fracture replication

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• Lipid-digesting

enzymes that cannot

penetrate the plasma

membrane and are

subsequently only

able to digest lipids

that reside in the

external monolayer of

the bilayer.

Membrane Asymmetry

SM, sphingomyelin; PC, phosphatidylcholine; PS, phosphatidylserine; PE, phosphatidylethanolamine; PI, phosphatidylinositol; Cl, cholesterol

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2.2 Transmembrane Transport

a pure phospholipid

bilayer

• Plasma membrane is semipermeable

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2.2.1 Overview of trans-membrane transport

Property Passive Diffusion Facilitated Diffusion Active Transport Cotransport

requiring specific transport protein

No Yes Yes Yes

Solute transported against its gradient

No No Yes Yes

Coupled to ATP hydrolysis

No No Yes No

Driven by movement of a ion down its gradient

No No No Yes

ExamplesO2, CO2, steroid hormones, many drugs

Glucose and amino acids (uniporters); ions and water (channels)

Ions, small hydrophilic molecules, lipids (ATP- powered pumps)

Glucose and amino acids (symporters); various ions and sucrose (antiporters)

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Types of trans-membrane transport

Active transport Passive transport

transport proteinschannel proteins

transporters

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Three types of transporters

Uniport symport antiport

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2.2.2 Passive transport

• no metabolic energy is expended;

• no specific transport proteins needed;

• molecules move down its chemical concentration

gradient.• Diffusion rate is determined by:

– concentration gradient across the layer– hydrophobicity– size – electric potential across the membrane

Passive diffusion (simple diffusion)

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• polar molecules, ions and water, transport across

membrane by a protein-mediated movement

• exhibits the following distinguishing properties from

passive diffusion:

− The rate is far higher than passive diffusion

− The partition coefficient K is irrelevant

− Occurs via a limited number of uniporter molecules

− Transport is specific.

Facilitated Diffusion

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A typical example of facilitated diffusion

Uniporter mediates passive movement of a glucose solute.

GLUT1 facilitates the unidirectional transport of glucose down its concentration gradient

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• assist diffusion

• water, ions and hydrophilic small molecules

• down concentration or electric potential gradients

• form a hydrophilic passageway across the

membrane

Ion channel

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Ion channel

The structure and ion selectivity of a bacteria K+ channel.

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Ion channel

Channel proteins • nongated channels• gated channels

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Some examples of ion channels

Channel Location FunctionsK+ leakage channel The plasma membrane of

most animalsKeep resting potential

Voltage-gated Na+ channel The plasma membrane of neural axon

Produce action potenpial

Voltage-gated K+ channel The plasma membrane of neural axon

Resume resting potential after starting action potenpial

Voltage-gated Ca2+ channel The plasma membrane of nerve terminal

Activate releasing of nerve transmitter

Acetylcholine acceptor Acetylcholine-gated Na+ and Ca2+ channel)

The plasma membrane of muscle cells (The link-end of nerve and muscle)

Excitable synaptic transmission of signals (transform chemical signal to electric one in target cells)

GABA acceptor (GABA- gated Cl- channel)

The plasma membrane of many nerve cells (at synapse)

Inhibitory synaptic transmission of signals

Stress-gated positive ion channel

Auditory hair cells in inner ear

Detect the jutter of voice

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2.2.3 Active transport

• mediated by a specific membrane proteins• against their concentration gradient • need the energy supply

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• Four classes: P, V, F and ABC (ATP-binding cassette transporter)

• Energy supply is coupled to the hydrolysis of ATP

ATP-driven pumps

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• Examples of four classes of ATP pumps

Class Examples

P-Class Plasma membrane of plants, fungi, bacteria (H+ pump), Plasma membrane of higher eukaryotes (Na+/K+ pump), Apical plasma membrane of mammalian stomach (H+/K+ pump), Plasma membrane of all eukaryotic cells (Ca2+ pump), Sarcoplasmic reticulum membrane in muscle cells (Ca2+ pump)

V-Class Vacuolar membranes in plants, yeast, other fungi, Endosomal and lysosmal membranes in animal cells, Plasma membrane of osteoclasts and some kidney tubule cells.

F-Class Bacterial plasma membrane, Inner mitochondrial membrane, Thylakoid membrane of chloroplast

ABC-Class

Bacterial plasma membranes (amino acid, sugar, and peptide permeases), Mammalian plasma membranes (transporters of phospholipids, small lipophilic drugs, cholesterol, other small molecules)

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• two types: symporter and antiporter

• coupled to an energetically favorable reaction

• use the energy stored in an electrochemical

gradient

• Establishment of these electrochemical

gradients is energy consuming

• secondary active transport.

Cotransporters

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Two types of carriers enable gut epithelial cells to transfer glucose and amino acid across the gut lining

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Comparative of symports in animal and plant cells

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2.3 Cell adhesion molecules and cell junction

• Cell–cell adhesion

• Cell-matrix adhesion

• Cell adhesion molecules (CAMs)

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Three models of cell adhesion

23/4/21 58Major families of CAMs

2.3.1 CAMs

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Cell Adhesion Molecules Family Ligands recognized Stable cell junction

Cadherins Homophilic interactionsAdherens junctions and desmosomes

IntegrinsExtracellular matrix

Focal adhesions and hemidesmosomes

Members of Ig superfamily

No

Selectins Carbohydrates No

Ig superfamilyIntegrins No

Homophilic interactions No

Cadherin

Homophilic interactions

Selectins

Recognition of specific carbohydrates Heterophilic interactions

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Function of lectins in cell adhesion

Carbohydrate chain recognition

CAMs adhesion

Ig superfamily

Homophilic /heterophilic interactions

• Receptor for ECM

• Extracellular domain

interacts with ECM

protein

• Intracellular tail

interacts with actin

Heterophilic interactions

integrin

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2.3.2 Cell Junctions

Three types of cell junctions:

Tight junction

Anchoring junction

Gap junction

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Cell Junctions

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Tight junction

A current model of a tight junction

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Function of tight junction

• form seals that prevent the free passage of molecules between the

cells of epithelia;

• prevent leakage of molecules across the epithelium though the

gaps between cells;

• separate the apical and basolateral domains of plasma membrane

by preventing the free diffusion of lipids and proteins between them

and help establish and maintain cell polarity.

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Tight junction and cell polarity

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• Cell-cell anchoring junction

●Adherens junction

●Desmosome

• Cell-Matrix anchoring junction

●Focal adhesion

●Hemidesmosome

Anchoring junction

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Adherens Junction

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Desmosomes

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Focal adhesion

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Hemidesmosomes

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Function of anchoring junction

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An overview of the types of interactions involving the cell surface.

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A summary of junctional and nonjunctional adhesive mechanisms

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• In animal

●connexon:

Six connexins assemble to form a connexon

with an open hydrophilic pore in its center;

Connexon in one cell aligns with the connexon

of adjacent cell forming a channel.

• In plant

●plasmodesmata

Gap junction

Function of gap junction

• Mechanical connection；

• Electrical coupling ：

• Matebolic coupling: (<1000 Dolton)

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Gap junction in animals

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Gap junction in plants

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2.4 Extracellular Matrix and Cell Wall

An overview of cells interact with their environment

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2.4.1 Extracellular Matrix

The extracellular matrix (ECM) is a complex meshwork of

proteins and polysaccharides secreted by cells into the

spaces between them. The ECM plays important roles in

cell-cell signaling, wound repair, cell adhesion and tissue

function.

Three major component of ECM

proteoglycan

structure protein

adhesive protein

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proteoglycan: matrix of ECM

core protein + glycosaminoglycans (GAGs)

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Glycosaminoglycans

• a repeating disaccharide

with a -A-B-A-B-A-

structure

• disaccharides include∶

chondroitin sulfate

hyaluronic acid

keratan sulfate

heparan sulfate

…..

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hyaluronic acida nonsulfated GAG, assemble proteoglycans into huge complexes by linkage of the core proteins.

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Collagens and elastins: structure protein of ECMCollagen

•water-insoluble fibrous glycoproteins, the backbone

proteins for ECM.

•most abundant protein in the human body (> 25 percent of

all protein) with high tensile strength:

collagen fiber (Φ1 mm) suspending 10 kg.

•produced primarily by fibroblasts, and also by smooth

muscle cells and epithelial cells.

•tropocollagen consisting of three polypeptide chains

(Gly-X-Y)n

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Structure of Collagens

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Structural features of collagens

• All collagen molecules are trimers consisting of three polypeptide chains, called chains.

• Along at least part of their length, the three polypeptide chains of a collagen molecule are wound around each other to form a unique, rod-like triple helix

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◆Assembling of collagen

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Structure of elastin

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adhesive proteins

Fibronectin (FN)

RGD motif (for integrin binding) mediate cell

adhesion to ECM.

Laminin (LN)

Key structural component of basal lamina, a

specialized ECM

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Fibronectin (FN)

Laminin (LN)

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2.4.2 Connecting Cells to the ECM

The components of the ECM, such as fibronectin, laminin, proteoglycans, and collagen are capable of binding to receptors situated on the cell surface.

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2.4.2 Connecting Cells to the ECM

• The ECM interacts with the surface of the cell

through fibronectin

• Cells attach to the ECM by means of integrins

• Integrins are receptor proteins which are of

crucial importance

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the integrins binding to RGD motif (Arg-Gly-Asp) in Fibronectin

The most important family of receptors that attach cells to their extracellular microenvironment is the integrins.

Basement membrane (Basal lamina)

Structural components:

•laminin ： main component, organizer

• Ⅳ type collagen

•entactin

•perlecan

a specialized ECM structure underlies the epithelium,

which lines the cavities and surfaces of organs.

Structure of basement membrane

• Cellulos

• Hemicellulose

• Pectin

• Lignin

• glycoprotein

2.4.3 CELL WALLS

structural components of plant cell wall:

90% sugar

CELL WALLS

Layers of plant cell walls

structural components of bacterial cell wall:

murein: peptidoglycan

? Function of Penicillin Gram-positive vs Gram-negative

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bacterial cell wall and cytoplasmic membrane