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Cell Membrane Structure and Function. Membranes and Cell Transport. All cells are surrounded by a plasma membrane. Cell membranes are composed of a lipid bilayer with globular proteins embedded in the bilayer.

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membranes and cell transport
Membranes and Cell Transport
  • All cells are surrounded by a plasma membrane.
  • Cell membranes are composed of a lipid bilayer with globular proteins embedded in the bilayer.
  • On the external surface, carbohydrate groups join with lipids to form glycolipids, and with proteins to form glycoproteins. These function as cell identity markers.
fluid mosaic model
Fluid Mosaic Model

Extracellular fluid

Glycoprotein

Glycolipid

Carbohydrate

Cholesterol

Transmembrane

proteins

Peripheral

protein

Cytoplasm

Filaments of

cytoskeleton

  • In 1972, S. Singer and G. Nicolson proposed the Fluid Mosaic Model of membrane structure
phospholipid bilayer
Phospholipid Bilayer

Polar

hydro-philic

heads

Nonpolar

hydro-phobic

tails

Polar

hydro-philic

heads

  • Mainly 2 layers of phospholipids; the non-polar tails point inward and the polar heads are on the surface.
  • Contains cholesterol in animal cells.
  • Is fluid, allowing proteins to move around within the bilayer.
phospholipids
Phospholipids

Choline

Hydrophilic head

Phosphate

Glycerol

Hydrophobic tails

Fatty acids

Hydrophilic

head

Hydrophobic

tails

Space-filling model

Structural formula

Phospholipid symbol

  • In phospholipids, two of the –OH groups on glycerol are joined to fatty acids. The third –OH joins to a phosphate group which joins, in turn, to another polar group of atoms.
  • The phosphate and polar groups are hydrophilic (polar head) while the hydrocarbon chains of the 2 fatty acids are hydrophobic (nonpolar tails).
membrane components
Membrane Components

Cholesterol

  • Membrane carbohydrates
    • Interact with the surface molecules of other cells, facilitating cell-cell recognition
    • Cell-cell recognition is a cell’s ability to distinguish one type of neighboring cell from another
  • Steroid Cholesterol
    • Wedged between phospholipid molecules in the plasma membrane of animal cells.
    • At warm temperatures (such as 37°C), cholesterol restrains the movement of phospholipids and reduces fluidity.
    • At cool temperatures, it maintains fluidity by preventing tight packing.
    • Thus, cholesterol acts as a “temperature buffer” for the membrane, resisting changes in membrane fluidity as temperature changes.
membrane components1
Membrane Components

Fibers of extracellular

matrix (ECM)

EXTRACELLULAR

SIDE

Glycoprotein

N-terminus

Carbohydrate

Glycolipid

Microfilaments

of cytoskeleton

C-terminus

Peripheral

protein

Cholesterol

Integral

protein

CYTOPLASMIC

SIDE

a Helix

  • Membrane Proteins
    • A membrane is a collage of different proteins embedded in the fluid matrix of the lipid bilayer
    • Peripheral proteins are appendages loosely bound to the surface of the membrane
    • Integral proteins penetrate the hydrophobic core of the lipid bilayer
    • Many are transmembrane proteins, completely spanning the membrane
functions of cell membranes
Functions of Cell Membranes
  • Regulate the passage of substance into and out of cells and between cell organelles and cytosol
  • Detect chemical messengers arriving at the surface
  • Link adjacent cells together by membrane junctions
  • Anchor cells to the extracellular matrix
6 major functions of membrane proteins
6 Major Functions Of Membrane Proteins

ATP

Enzymes

Signal

Receptor

  • Transport. (left) A protein that spans the membrane may provide a hydrophilic channel across the membrane that is selective for a particular solute. (right) Other transport proteins shuttle a substance from one side to the other by changing shape. Some of these proteins hydrolyze ATP as an energy ssource to actively pump substances across the membrane
  • Enzymatic activity. A protein built into the membrane may be an enzyme with its active site exposed to substances in the adjacent solution. In some cases, several enzymes in a membrane are organized as a team that carries out sequential steps of a metabolic pathway.
  • Signal transduction. A membrane protein may have a binding site with a specific shape that fits the shape of a chemical messenger, such as a hormone. The external messenger (signal) may cause a conformational change in the protein (receptor) that relays the message to the inside of the cell.
slide10

Glyco-

protein

6 Major Functions Of Membrane Proteins

4.

Cell-cell recognition. Some glyco-proteins serve as

identification tags that are specifically recognized

by other cells.

5.

Intercellular joining. Membrane proteins of adjacent cells

may hook together in various kinds of junctions, such as

gap junctions or tight junctions

Attachment to the cytoskeleton and extracellular matrix

(ECM). Microfilaments or other elements of the

cytoskeleton may be bonded to membrane proteins,

a function that helps maintain cell shape and stabilizes

the location of certain membrane proteins. Proteins that

adhere to the ECM can coordinate extracellular and

intracellular changes

6.

slide11

Functions of Plasma Membrane Proteins

Outside

Plasma

membrane

Inside

Transporter

Enzyme

Cell surface

receptor

Cell surface identity

marker

Attachment to the

cytoskeleton

Cell adhesion

cell junctions
Cell Junctions
  • Long-lasting or permanent connections between adjacent cells, 3 types of cell junctions:
    • Tight junction
    • Anchoring junction
    • Communicating junction
tight junctions
Tight Junctions
  • Connect cells into sheets. Because these junctions form a tight seal between cells, in order to cross the sheet, substances must pass through the cells, they cannot pass between the cells.

Tight

junction

anchoring junctions
Anchoring Junctions

Plasma

membranes

Intracellular

attachment

proteins

Cell

1

Cell

2

Cytoskeletal

filament

Inter-

cellular

space

Transmembrane

linking proteins

Extracellular

matrix

  • Attach the cytoskeleton of a cell to the matrix surrounding the cell, or to the cytoskeleton of an adjacent cell.
communicating gap junctions
Communicating (Gap) Junctions

Two adjacent connexons

form a gap junction

Connexon

Adjacent plasma

membranes

Intercellular space

  • Link the cytoplasms of 2 cells together, permitting the controlled passage of small molecules or ions between them.
membrane carbohydrates
Membrane Carbohydrates
  • Membrane carbohydrates interact with the surface molecules of other cells, facilitating cell-cell recognition
  • Cell-cell recognition is a cell’s ability to distinguish one type of neighboring cell from another
membrane transport
Membrane Transport
  • The plasma membrane is the boundary that separates the living cell from its nonliving surroundings
  • In order to survive, A cell must exchange materials with its surroundings, a process controlled by the plasma membrane
  • Materials must enter and leave the cell through the plasma membrane.
  • Membrane structure results in selective permeability, it allows some substances to cross it more easily than others
passive transport
Passive Transport
  • Passive transport is diffusion of a substance across a membrane with no energy investment
  • 4 types
    • Simple diffusion
    • Dialysis
    • Osmosis
    • Facilitated diffusion
diffusion
Diffusion
  • The net movement of a substance from an area of higher concentration to an area of lower concentration - down a concentration gradient
  • Caused by the constant random motion of all atoms and molecules
  • Movement of individual atoms & molecules is random, but each substance moves down its own concentration gradient.
slide 3 21
Slide 3.21

Solutions and Transport

  • Solution – homogeneous mixture of two or more components
    • Solvent – dissolving medium
    • Solutes – components in smaller quantities within a solution
  • Intracellular fluid – nucleoplasm and cytosol
  • Extracellular fluid
    • Interstitial fluid – fluid on the exterior of the cell within tissues
    • Plasma – fluid component of blood
slide21

Diffusion

Random movement leads to net movement down a concentration gradient

Lump

of sugar

Water

No net movement at equilibrium

diffusion across a membrane
Diffusion Across a Membrane

Equilibrium

Net diffusion

Net diffusion

  • The membrane has pores large enough for the molecules to pass through.
  • Random movement of the molecules will cause some to pass through the pores; this will happen more often on the side with more molecules. The dye diffuses from where it is more concentrated to where it is less concentrated
  • This leads to a dynamic equilibrium: The solute molecules continue to cross the membrane, but at equal rates in both directions.
diffusion across a membrane1
Diffusion Across a Membrane
  • Two different solutes are separated by a membrane that is permeable to both
  • Each solute diffuses down its own concentration gradient.
  • There will be a net diffusion of the purple molecules toward the left, even though the total solute concentration was initially greater on the left side

Equilibrium

Net diffusion

Net diffusion

Net diffusion

Equilibrium

Net diffusion

the permeability of the lipid bilayer
The Permeability of the Lipid Bilayer
  • Permeability Factors
    • Lipid solubility
    • Size
    • Charge
    • Presence of channels and transporters
  • Hydrophobic molecules are lipid soluble and can pass through the membrane rapidly
  • Polar molecules do not cross the membrane rapidly
  • Transport proteins allow passage of hydrophilic substances across the membrane
slide25
Passive Transport Processes
  • 3 special types of diffusion that involve movement of materials across a semipermeable membrane
  • Dialysis/selective diffusion of solutes
    • Lipid-soluble materials
    • Small molecules that can pass through membrane pores unassisted
  • Facilitated diffusion - substances require a protein carrier for passive transport
  • Osmosis – simple diffusion of water
osmosis
Osmosis
  • Diffusion of the solvent across a semipermeable membrane.
  • In living systems the solvent is always water, so biologists generally define osmosis as the diffusion of water across a semipermeable membrane:
slide27

Lower

concentration

of solute (sugar)

Higher

concentration

of sugar

Same concentration

of sugar

Selectively

permeable mem-

brane: sugar mole-

cules cannot pass

through pores, but

water molecules can

Water molecules

cluster around

sugar molecules

More free water

molecules (higher

concentration)

Fewer free water

molecules (lower

concentration)

Osmosis

Water moves from an area of higher

free water concentration to an area

of lower free water concentration

osmotic pressure
Osmotic Pressure
  • Osmotic pressure of a solution is the pressure needed to keep it in equilibrium with pure H20.
  • The higher the [solutes] in a solution, the higher its osmotic pressure.
  • Tonicity is the ability of a solution to cause a cell to gain or lose water – based on the concentration of solutes
my definition of osmosis
My definition of Osmosis
  • Osmosis is the diffusion of water across a semi-permeable membrane from a hypotonic solution to a hypertonic solution
tonicity
Tonicity

Hypotonic solution

Hypertonic solution

Isotonic solution

H2O

H2O

H2O

H2O

Normal

Shriveled

Lysed

  • If 2 solutions have equal [solutes], they are called isotonic
  • If one has a higher [solute], and lower [solvent], is hypertonic
  • The one with a lower [solute], and higher [solvent], is hypotonic
facilitated diffusion
Facilitated Diffusion

EXTRACELLULAR

FLUID

Solute

Carrier protein

Channel protein

Solute

CYTOPLASM

  • Diffusion of solutes through a semipermeable membrane with the help of special transport proteins i.e. large polar molecules and ions that cannot pass through phospholipid bilayer.
  • Two types of transport proteins can help ions and large polar molecules diffuse through cell membranes:
    • Channel proteins – provide a narrow channel for the substance to pass through.
    • Carrier proteins – physically bind to the substance on one side of membrane and release it on the other.
facilitated diffusion1
Facilitated Diffusion
  • Specific – each channel or carrier transports certain ions or molecules only
  • Passive – direction of net movement is always down the concentration gradient
  • Saturates – once all transport proteins are in use, rate of diffusion cannot be increased further
active transport
Active Transport
  • Uses energy (from ATP) to move a substance against its natural tendency e.g. up a concentration gradient.
  • Requires the use of carrier proteins (transport proteins that physically bind to the substance being transported).
  • 2 types:
    • Membrane pump (protein-mediated active transport)
    • Coupled transport (cotransport).
membrane pump
Membrane Pump
  • - A carrier protein uses energy from ATP to move a substance across a membrane, up its concentration gradient:
the sodium potassium pump
The Sodium-potassium Pump
  • One type of active transport system

[Na+] high

[K+] low

Na+

Na+

1. Cytoplasmic Na+ binds to the sodium-potassium pump.

2. Na+ binding stimulates

phosphorylation by ATP.

Na+

Na+

EXTRACELLULAR

FLUID

Na+

ATP

[Na+] low

[K+] high

P

Na+

ADP

CYTOPLASM

Na+

Na+

6. K+ is released and Na+

sites are receptive again;

the cycle repeats.

3. Phosphorylation causes the

protein to change its conformation, expelling Na+ to the outside.

Na+

K+

P

K+

5. Loss of the phosphate

restores the protein’s

original conformation.

K+

4. Extracellular K+ binds to the

protein, triggering release of the

Phosphate group.

K+

K+

K+

P i

P

P i

coupled transport
Coupled transport

2 stages:

  • Carrier protein uses ATP to move a substance across the membrane against its concentration gradient. Storing energy.
  • Coupled transport protein allows the substance to move down its concentration gradient using the stored energy to move a second substance up its concentration gradient:
bulk transport
Bulk Transport
  • Allows small particles, or groups of molecules to enter or leave a cell without actually passing through the membrane.
  • 2 mechanisms of bulk transport: endocytosis and exocytosis.
endocytosis
Endocytosis
  • The plasma membrane envelops small particles or fluid, then seals on itself to form a vesicle or vacuole which enters the cell:
    • Phagocytosis
    • Pinocytosis
slide39

Phagocytosis

The substance engulfed is a solid particle

slide41

Pinocytosis

Thesubstance engulfed is a liquid

exocytosis
Exocytosis
  • The reverse of endocytosis
  • During this process, the membrane of a vesicle fuses with the plasma membrane and its contents are released outside the cell:
cells communication
Cells Communication
  • Direct contact
  • Paracrine signaling
  • Endocrine signaling
  • Synaptic signaling
direct contact
Direct Contact

Adjacent connexons

form a gap junction

  • Cells touch each other and signal molecules travel through special connections called communicating junctions
  • Communicating Junctions link the cytoplasms of 2 cells together, permitting the controlled passage of small molecules or ions between them.
local and long distance cell communication in animals
Local and long-distance cell communication in animals

Local signaling

Long-distance signaling

Blood

vessel

Endocrine cell

Target cell

Electrical signal

along nerve cell

triggers release of

neurotransmitter

Neurotransmitter

diffuses acrosssynapse

Secretory

vesicle

Secreting

cell

Hormone travels

in bloodstream

to target cells

Local regulator

diffuses through

extracellular fluid

Target

cell

Target cell

is stimulated

(b) Synaptic signaling. A nerve cell releases neurotransmitter molecules into a synapse, stimulating the target cell.

(a) Paracrine signaling. A secreting cell acts on nearby target cells by discharging molecules of a local regulator (a growth factor, for example) into the extracellular fluid.

(c) Hormonal signaling. Specialized endocrine cells secrete hormones into body fluids, often the blood. Hormones may reach virtually all body cells.

cell signaling
Cell Signaling

EXTRACELLULAR

FLUID

CYTOPLASM

Plasma membrane

3

1

2

Reception

Transduction

Response

Receptor

Activation

of cellular

response

Relay molecules in a signal transduction pathway

Signal

molecule

  • The cells of a organism communicate with each other by releasing signal molecules that bind to receptor proteins located either on or inside of target cells.
  • Three stages of cell signaling:
    • Reception - each target cell has receptors that detect a specific signal molecule and binds to it
    • Transduction – binding of the signal molecule changes the receptor protein in some way that initiates transduction or conversion of the signal to a form that can bring about a specific cellular response
    • Response – transduced signal triggers a specific cellular response, any cell activity
reception
Reception
  • A signal molecule binds to a receptor protein, causing it to change shape
  • The binding between signal molecule (ligand) and receptor is highly specific
  • A conformational change in a receptor
    • Is often the initial transduction of the signal
receptors
Receptors
  • Intracellular receptors
    • Some signal molecules that are small or hydrophobic can pass through the plasma membrane and bind to receptors located inside the cell
    • Intracellular receptors are cytoplasmic or nuclear proteins
  • Cell surface receptors. - Signal molecules that cannot pass through the plasma membrane bind to receptors located on the surface of the membrane
intracellular receptors
Intracellular Receptors
  • Gene Regulators
    • Signal molecule joins to the receptor, the receptor changes shape and a DNA binding site is exposed.
    • The DNA binding site joins to a specific segment of DNA and activates (or suppresses) a particular gene
  • Enzyme Receptor
    • These receptors function as enzymes – proteins that catalyze (speed up) specific chemical reactions.
    • When a signal molecule joins to the receptor, the receptor’s catalytic domain is activated (or deactivated).
steroid hormone interacting with an intracellular receptor
 Steroid hormone interacting with an intracellular receptor

Hormone

(testosterone)

EXTRACELLULAR

FLUID

The steroid

hormone testosterone

passes through the

plasma membrane.

4

3

2

5

1

Plasma

membrane

Testosterone binds

to a receptor protein

in the cytoplasm,

activating it.

Receptor

protein

Hormone-

receptor

complex

The hormone-

receptor complex

enters the nucleus

and binds to specific

genes.

DNA

The bound protein

stimulates the

transcription of

the gene into mRNA.

mRNA

NUCLEUS

New protein

The mRNA is

translated into a

specific protein.

CYTOPLASM

signal pathways membrane receptors
Signal Pathways: Membrane Receptors
  • Receptors located on the surface of the membrane
    • Chemical or ligand-gated ion channels
    • Enzymatic receptors
    • G-protein-linked receptors

Figure 6-5

chemically gated ion channels
Chemically Gated Ion Channels

Gate close

Gate

Closed

Signalmolecule(ligand)

Ions

Ligand-gated

ion channel receptor

Plasma Membrane

Gate open

Cellularresponse

Gate close

  • Open or close when the signal molecule binds to the channel.
enzymatic receptors
Enzymatic Receptors

Signal-binding site

Signalmolecule

Signal molecule

 Helix in the

Membrane

Tyr

Tyr

Tyr

Tyr

Tyrosines

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Receptor tyrosinekinase proteins(inactive monomers)

Dimer

CYTOPLASM

Activatedrelay proteins

Cellularresponse 1

P

P

Tyr

Tyr

Tyr

Tyr

P

P

Tyr

Tyr

Tyr

Tyr

P

P

P

Tyr

Tyr

Tyr

Tyr

P

Tyr

Tyr

Tyr

Tyr

Cellularresponse 2

P

P

P

Tyr

Tyr

Tyr

Tyr

P

Tyr

Tyr

Tyr

Tyr

6 ATP 6 ADP

Activated tyrosine-

kinase regions

(unphosphorylated

dimer)

Fully activated receptor

tyrosine-kinase

(phosphorylated

dimer)

Inactiverelay proteins

  • Embedded in the plasma membrane, with their catalytic site exposed inside the cell.
  • Catalytic site activated when the signal molecule joins to the receptor.
  • Function as protein kinases (enzymes that phosphorylate proteins.)
g protein linked receptors
G-protein-linked Receptors

Signal-binding site

Segment that

interacts with

G proteins

Inactive

enzyme

Activatedreceptor

G-protein-linked

receptor

Signal molecule

Plasma Membrane

GDP

G-protein(inactive)

GTP

GDP

CYTOPLASM

Enzyme

Activated

enzyme

GTP

GDP

Pi

Cellular response

  • Signal molecule joins to a receptor, the receptor activates a G protein
  • The activated G protein can then activate an ion channel or enzyme in the plasma membrane.
second messengers
Second Messengers
  • Some enzymatic receptors and most G-protein-linked receptors relay their message into the cell by activating other molecules or ions inside the cell.
  • These molecules and ions, called second messengers, transmit the message within the cell.
  • The 2 most common second messengers are cAMP and Ca++
camp second messenger g protein signaling pathway
cAMP Second MessengerG-protein-signaling pathway

First messenger

(signal molecule

such as epinephrine)

Adenylyl

cyclase

G protein

GTP

G-protein-linked

receptor

ATP

Second

messenger

cAMP

Protein

kinase A

Cellular responses

  • Signal molecule binds to surface receptor
  • Surface receptor activates a G protein
  • G protein activates the membrane-bound enzyme, adenylyl cyclase
  • Adenylyl cyclase catalyzes synthesis of camp, which binds to a target protein
  • Target protein initiates cellular change
cyclic amp
Cyclic AMP

NH2

NH2

NH2

N

N

N

N

N

N

N

N

N

N

N

O

O

O

N

O

Adenylyl cyclase

Phoshodiesterase

CH2

O

HO

Ch2

P

–O

O

P

O

P

P

O

CH2

O

O

O

O

O

O

O

O

O

P

Pyrophosphate

H2O

O

O

P

P

i

OH

OH

OH

OH

OH

ATP

Cyclic AMP

AMP

calcium and ip 3 in signaling pathways
Calcium and IP3 in signaling pathways

2

4

3

1

5

6

A signal molecule binds

to a receptor, leading to

activation of phospholipase C.

DAG functions as

a second messenger

in other pathways.

Phospholipase C cleaves a

plasma membrane phospholipid

called PIP2 into DAG and IP3.

EXTRA-

CELLULAR

FLUID

Signal molecule

(first messenger)

G protein

DAG

GTP

PIP2

G-protein-linked

receptor

Phospholipase C

IP3

(second messenger)

IP3-gated

calcium channel

Endoplasmic

reticulum (ER)

Various

proteins

activated

Cellularresponses

Ca2+

Ca2+

(second

messenger)

CYTOSOL

The calcium ions

activate the next

protein in one or more

signaling pathways.

IP3 quickly diffuses through

the cytosol and binds to an IP3–

gated calcium channel in the ER

membrane, causing it to open.

Calcium ions flow out of

the ER (down their con-

centration gradient), raising

the Ca2+ level in the cytosol.

  • Signal molecule binds to surface receptor
  • Surface receptor activates a G protein
  • G protein activates the membrane-bound enzyme, phospholipase C
  • Phospholipase C catalyzes synthesis of inositol triphosphate (IP3), which stimulates release of Ca++ from ER
  • Released Ca++ initiates cellular change
signal pathway signal transduction
Signal Pathway: Signal Transduction

Steps of a cascade

Steps of signal transduction pathway form a cascade

Figure 6-9

a phosphorylation cascade
 A Phosphorylation Cascade

Signal molecule

Receptor

Activated relay

molecule

A relay molecule

activates protein kinase 1.

3

2

5

1

4

Active protein kinase 1

transfers a phosphate from ATP

to an inactive molecule of

protein kinase 2, thus activating

this second kinase.

Inactive

protein kinase

1

Active

protein

kinase

1

Inactive

protein kinase

2

Active protein kinase 2

then catalyzes the phos-

phorylation (and activation) of

protein kinase 3.

ATP

Phosphorylation cascade

P

ADP

Active

protein

kinase

2

PP

P

i

Inactive

protein kinase

3

ATP

Enzymes called protein

phosphatases (PP)

catalyze the removal of

the phosphate groups

from the proteins,

making them inactive

and available for reuse.

P

ADP

Finally, active protein

kinase 3 phosphorylates a

protein (pink) that brings

about the cell’s response to

the signal.

Active

protein

kinase

3

PP

P

i

Inactive

protein

ATP

P

ADP

Active

protein

Cellular

response

PP

i

signal pathways signal amplification
Signal Pathways: Signal Amplification
  • Transducers convert extracellular signals into intracellular messages which create a response

Figure 6-7

signal amplification
Signal Amplification

Reception

Binding of epinephrine to G-protein-linked receptor (1 molecule)

Transduction

Inactive G protein

Active G protein (102 molecules)

Inactive adenylyl cyclase

Active adenylyl cyclase (102)

ATP

Cyclic AMP (104)

Inactive protein kinase A

Active protein kinase A (104)

Inactive phosphorylase kinase

Active phosphorylase kinase (105)

Inactive glycogen phosphorylase

Active glycogen phosphorylase (106)

Response

Glycogen

Glucose-1-phosphate(108 molecules)

  • Stimulation of glycogen breakdown in a liver cell by epinephrine
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