Transmembrane Transport & Cell-to-Cell Communication

Compiled by: Prof. Dr. Herbert Sipahutar, M.Sc.

Program Magister Pendidikan Biologi

Sekolah Pascasarjana

Universitas Negeri Medan

2009

Membrane Permeability
The Cell Membrane is a Semi-Permeable membrane. Separates the inside of the cell from the outside. Regulates what enters and leaves the cell.

FUNCTION
So how important is the cell membrane? Helps maintain a stable internal environment, which is called HOMEOSTASIS. 5 important functions: 1. Selectivity 2. Recognition Ability 3. Export of wastes and cell products 4. Import Nutrients 5. Change ability according to its environment

Protein

Phospholip d bilayer

Cell Transport
DIFFUSION -- is the net movement of particles from high concentration to low concentration.

Osmosis
2. OSMOSIS - is the diffusion of water molecules through a membrane from an area of high to low. A. Isotonic solution - equal concentrations B. Hypotonic solution Higher Concentration of water compared to the inside of cell. (cell gets bigger) C. Hypertonic solution - Lower Concentration of water compared inside of the cell. (cell shrinks)

Iso, hyper, hypo

More Cellular Transport

3. PASSIVE TRANSPORT the movement of substances across the membrane without energy using a carrier or channel protein. HIGH LOW

4. ACTIVE TRANSPORT the movement of a substance across the membrane with energy against the concentration gradient. LOW HIGH

5. The movement of LARGE PARTICLES a. ENDOCYTOSIS - the cell surrounds and takes in material b. EXOCYTOSIS- opposite of endocytosis.

No turgur

Plasmolysis 100X

Plasmolysis 400x

4 ways to penetrate the Cell Membrane

Simple Diffusion Passive transport (facilitated diffusion)

Active transport (energydependent) Receptor-mediated endocytosis

Simple Diffusion
Initial Final

High
Low

GA o' GA

= the chemical potential of A

= chemical potential of standard state
= GA(in) - GA(out) (final - initial) = RTln GA

(also called the partial molar free energy)

GA GAo = RTln[A] (free energy varies with conc. A)

GA GA

= GA(in) - GA(out) If [A]out is > [A] in,

[A]in
[A]out exergonic endergonic

Thus:

is negative

If [A]out is < [A] in, If [A]out = [A]in,

GA is positive GA is zero

Thermodynamics (ENERGY) of Transport

Diffusion Rule:

A(out)

A(in)

Free energy is released when a solute moves from an area of high concentration to low concentration

Spontaneous

(out)
High

(in)
Low Final state Initial state =G = negative

GA (in)

<

GA (out)

(out)

(in)

Balanced
Rule:

Free energy change is zero when the concentration of A on both sides is the same GA (in) = GA (out) Final state Initial state =G = 0

(out) GA (in)
>

(in) GA (out)

Final state Initial state =G= positive

Rule: When chemical potential of A(in) is greater than A(out), energy must be provided to drive A across the membrane, i.e., make free energy change negative

Energy = ATP or a proton gradient

Rule:
The movement of ions presents a separate challenge because not only must the mass difference (chemical potential) be taken into account, but also the charge differential (electrochemical potential)

electrochemical potential refers to the state of (+) (-) charges on both sides of the membrane The electrochemical potential is referred to as the membrane potential when dealing with cells

Chemical potential

GA

= GA(in) - GA(out)
and

= RTln

[A]in
[A]out

Electrochemical potential GA = GA(in) - GA(out) = ZAF Membrane potential Total Energy GA = RTln

[A]in
[A]out

+ ZAF

Text p398

Na Na +

+ + Na +

+ Na + + + Na + Na Na + + + +
Na Na

Na

+Na

_ Na + Na + _ + Na _ 15:1 (- 60 mV) [A]in 10 mM

150 mM

[A]out [0.010] = 8.314 x (310 K) x ln + (1) 96,500 x -0.06 volts [0.150] = 12.8 kJ/mole

GNa+

= RTln

+ ZAF

Na Na Na +

+ + Na + + + Na

Out
+

In _ _ _ (+ 60 mV)
Na + Na + Na + Na +

Na Na + + Na Na + +Na Na

+ + +

150 mM

10 mM + ZAF

GNa+

= RTln

[A]out [A]in

= 8.314 x (310 K) x ln = + 12.8 kJ/mole

[0.150] [0.010]

+ (1) 96,500 x +0.06 volts

 Out Cl Cl Cl + Cl Cl + Cl + Cl Cl Cl

In
_ _ _ (+ 60 mV)
Cl Cl

Cl

150 mM GCl-

10 mM + ZAF

= RTln

[A]in
[A]out

= 8.314 x (310 K) x ln

[0.010] + (1) 96,500 x +0.06 volts [0.150]

= 6.85 kJ/mole + 5.79 kJ/mol = 1.06 kJ/mol

 Out Cl Cl Cl + Cl Cl + Cl + Cl Cl Cl

In
_ _ _ ( 60 mV)
Cl Cl

Cl

150 mM GCl-

10 mM + ZAF

= RTln

[A]out
[A]in

= 8.314 x (310 K) x ln

[0.150] + (1) 96,500 x 0.06 volts [0.010]

= + 6.85 kJ/mole + ( 5.79 kJ/mol) = 1.19 kJ/mol

Facilitated Diffusion (Mediated Transport)

Modes of Transport

ATP-Driven (Active) Transport [Ca2+-ATPase]

Vesicle Trafficking
The secretory pathway The trans-Golgi network The signal hypothesis Protein targeting

Rule: Proteins destined for secretion from a cell or for relocation to a membrane or a specific organelle are synthesized on the rough endoplasmic reticulum (RER) Definition: The RER consists of ribosomes bound to membranes enclosing an internal hollow space or cisternae Selection: Proteins possess a signal sequence that is recognized by a receptor on the membrane Action: Proteins pass into the space and transit to the Golgi while entrapped in vesicles

Protein inserted in plasma membrane

Trans

Secretory granule

Golgi
Cis Golgi

Pre-lysosome

RER

Signal Hypothesis Proteins destined for secretion or transit to membranes and organelles, have a signal peptide that allows them to enter the RER cisternae

The signal peptide is recognized by a receptor called the signal recognition particle (SRP) on the RER membrane Signal sequences on the N-terminal represent a string of leucine-rich hydrophobic amino acids that allow the peptide to dock with the receptor
The signal peptide is removed after the peptide has penetrated the membrane

Signal Hypothesis
Docking

SRP

Signal Peptide cleaved SRP receptor

Lumen of cisternae

+NH

+NH

Rough Endoplasmic Reticulum

Carbohydrate

Transport of Ions and Small Molecules Across the Cell Membrane

Passive Diffusion

Gases, such as O2 & CO2, small uncharged polar molecules, urea & ethanol readily move by passive diffusion. Very few molecules and no ions can cross a pure phospholipid bilayer at appreciable rates by passive diffusion

Active Transport

ATP-powered pumps - Use energy of ATP hydrolysis

Facilitated Diffusion

Channel proteins transport water or specific types of ions and hydrophilic small molecules down their concentration gradient

Transporters (Carriers)

Uniporters
- transport a single molecule via facilitated diffusion

Transporters (contd)

Cotransporters Antiporters & Symporters

- couple the movement of one type of ion or milecule against its concentration gradient

Cell Membrane

The cell membrane performs many functionsincluding a protective barrier, a signal acceptor/ transmitter, and a gateway for needed materials (and unwanted wastes!).

Transport

Active Transport: Movement of materials against a concentration gradient.

Activity takes energy!!

Transport II

Passive Transport: Movement of particles by simple diffusion.

Passive is laid back!!!!

Facilitated Diffusion: The passive transport of materials across the plasma membrane with the aid of proteins.

Facilitated Diffusion

Facilitated diffusion is a common way of moving sugars (C6H12O6) and Amino Acids across a membrane. Also driven by a Concentration Gradient

A Type of Protein!!!

Endocytosis

Endocytosis: Process by which a cell surrounds and takes in material from its environment. Endocytosis = Enter

Exocytosis

Exocytosis: The expulsion or secretion of materials from a cell. Exocytosis = Exit!!!

__________ ____
_________ _________ ___ ___

Transport Proteins

Channel Proteins- Provide the openings through which small, dissolved particles (Especially Ions!) diffuse by passive transport!

Transport Proteins

Carrier Protein: Binds with a particle to be transported during Active Transport and has a shape that fits a specific molecule or Ion! (Atom with a charge!!!) Changes shape so that the particle can be moved and released on other side of membrane!!

Carrier Proteins!!!

Marker Proteins

Identifies this cell as belonging to YOU!!!

Why is it important that you are matched before receiving blood??

Receptor Proteins

Allows information to enter the cell!!

Causes a change inside the cell!! Ex. Hormones!!!

Cell Size Limitations

1.

Diffusion; Slow with distance!!! DNA: Not enough to support protein needs Cells surface area to volume: As a cells size increases, its volume increases much faster than its surface areaand yet a bigger cell would require more imports and exports!!!

The Final Product

The Cell Membrane

How does this relate to other areas in Biology??

1.

2.

3.

Your cells use these transport ideas to help maintain homeostasis; Oxygen/ Carbon Dioxide!... (Circulatory system/ Respiratory System!!!!) Nervous System (Nerve cells to communicate information!!!) Immune system (White blood cells engulfing foreign bodies!! Blood typing!!)

Cell Membrane Transport

1- Factors affecting transport - cell membrane - Chemical gradient - Electrical gradient - Rate of transport 2- Passive transport - Diffusion - Osmosis - Facilitated diffusion 3- Active transport - Pumps - phagocytosis - Endocytosis/exocytosis

Factors affecting transport: cell membrane

The cell needs to absorb and excrete various compounds throughout its life.

These compounds need to pass through the membrane which is made from a phospholipid bilayer

The phospholipid bilayer is formed by phospholipid molecules bipolar molecule: the fatty acid side is hydrophobic, the phosphoric side is hydrophilic

Stable phospholipid organizations

Figure 2.4

The membrane is permeable to:

H2O Gases (O2, CO2, N2) Lipids Small, neutral molecules (such as urea)

The membrane is impermeable to: - Small, charged molecules - large molecules such as amino acids, glucose and larger

these compounds must go through channels present in the membrane in order to enter or exit the cell

Factors affecting transport: Chemical gradient

Compound moves from an area of high concentration to low concentration (or concentration gradient) All compounds permeable to the phospholipid bilayer will move this way

Factors affecting transport: Electrical force

Positive ions are attracted to negative ions and vice versa Ions are repelled by ions of the same charge (+ against + and against -)

Figure 4.3

Movement across the cell membrane

Both chemical and electrical forces (electrochemical force) drive the movement of compounds across the cell membrane

Factors affecting the rate of transport

The rate of transport will depend on: - the concentration gradient - the compound permeability to the membrane - the type and number of charges present on the compound

Passive transport

Compounds will move from area of high concentration toward area of lower concentration No ATP is needed for this type of transport

DIFFUSION

diffusion process is a key factor in movement of substance across cell membranes and through the cytoplasm of the cell

66

DIFFUSION

movement of molecules from areas of high concentrations to areas of lower concentrations net movement of molecules occurs down the concentration gradient

67

DIFFUSION
Click here for animation

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DIFFUSION

Some molecules are able to diffuse without assistance or consumption of energy

oxygen, carbon dioxide and small molecules with no charge

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DIFFUSION

DIFFUSION

rate of diffusion is dependent on:

1) steepness of the concentration gradient 2) temperature 3) molecular size 4) electrical gradients 5) pressure gradients

- -- 71

++ ++

OSMOSIS

movement of water across a semipermeable membrane in response to solute concentration gradients

some small molecules (like water) pass readily through the cell membrane Other molecules like glucose must be pumped across the membrane

72

OSMOSIS

water concentration gradient is influenced by the number of molecules of solutes that are present on both sides of the membrane the direction in which water moves across the membrane is influenced by tonicity

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OSMOSIS

tonicity-relative concentrations of solutes in two fluids

water tends to move where solute concentrations are greatest

1) Isotonic=solute concentrations are equal

2) Hypotonic=least solute concentrations

3) Hypertonic=greatest solute concentrations

74

OSMOSIS

water molecules move from hypotonic solutions to hypertonic solutions cells require built in mechanisms for adjusting to differences in tonicity between cytoplasm and their surroundings

without them cells will:

1) shrivel (crenation) 2) burst (lyse)

75

OSMOSIS

76

Can you determine what type of solution these RBC have been subjected to?

OSMOSIS

77

ROUTES ACROSS CELL MEMBRANES

1) Diffusion / Osmosis

2) Protein Mediated Diffusion

3) Endocytosis and Exocytosis

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PROTEIN MEDIATED DIFFUSION

2) Protein mediated diffusion

glucose, large water soluble molecules and charged ions cannot diffuse freely across the cell membrane
A) B)

Passive Transport Active Transport

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PASSIVE TRANSPORT

molecules diffuse through non-selective channel proteins selective carrier proteins can move molecules of a solute across the cell membrane by binding and changing shape
passive transport occurs only down the concentration gradient
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ACTIVE TRANSPORT

transport occurs when carrier proteins receive an energy boost from ATP pump solutes across the cell membrane against the concentration gradient

ex: calcium pump, sodium-potassium pump

cytoplasm concentrations of K+ increase and Na+ decrease

81

TYPES OF MEMBRANE PROTEINS

1) Channel Proteins
2) Active Transport Proteins 3) Receptor Proteins 4) Recognition Proteins 5) Adhesion Proteins

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CHANNEL PROTEINS

does not require any energy investment by the cell

83

CHANNEL PROTEINS

most remain open at all times acts as a pore for water-soluble ions may have molecular gates

ex: nerve cells during nerve impulses

84

CHANNEL PROTEINS

1) molecules only move down the concentration gradient 2) does not require any energy input from the cell

85

FACILITATED DIFFUSION

Does not require energy

Highly selective Polar compounds such as sugars and amino acids Diffusion is down the concentration gradient

86

TYPES OF MEMBRANE PROTEINS

1) Channel Proteins

2) Active Transport Proteins

3) Receptor Proteins 4) Recognition Proteins 5) Adhesion Proteins

87

ACTIVE TRANSPORT PROTEINS

require energy to transport molecules

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ACTIVE TRANSPORT PROTEINS

1) molecules are pumped against their concentration gradient 2) requires an energy input from the cell

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ACTIVE TRANPORT PROTEINS

a change in shape allows bound substances to pass through the membrane some may require an energy input to actively pump substances across the membrane

90

TYPES OF MEMBRANE PROTEINS

1) Channel Proteins 2) Active Transport Proteins

3) Receptor Proteins
4) Recognition Proteins 5) Adhesion Proteins

91

RECEPTOR PROTEINS

have binding sites for hormones

ex: hormone somatotropin binds to receptors which triggers enzymes to activate cell growth and division

92

TYPES OF MEMBRANE PROTEINS

1) Channel Proteins 2) Active Transport Proteins 3) Receptor Proteins

4) Recognition Proteins
5) Adhesion Proteins

93

PASSIVE MECHANISMS Simple Diffusion

-Through Membrane

PASSIVE MECHANISMS CONT. THROUGH PORES

PASSSIVE MECHANISMS CONT. Carrier Facilitated Diffusion

PASSIVE MECHANISMS CONT.

OSMOSIS
Isotonic

Hypertonic (Plasmolysis) Shrink

Hypotonic (Plasmoptysis) Swell

Diffusion

Compounds move toward the area of lower concentration

Compounds permeable to the cell membrane will move through diffusion. (Compounds unable to pass through the membrane will only pass if membrane channels open)

Osmosis

Each compound obeys the law of diffusion However, some compounds are unable to cross the cell membrane (glucose, electrolytes) Water can cross will enter or exit the cell depending its concentration gradient

Note: the cell membrane is a semipermeable membrane

Solution tonicity

Isotonic solution: solution which has the same compound concentration as the cell Hypotonic solution: solution having a compound in lower concentration compared to the cell Hypertonic solution: solution having a compound in higher concentration compared to the cell

Facilitated diffusion

Some compounds are unable to diffuse through the membrane. They will be allow to cross if the membrane has proteins that can bind these compounds and enable to cross toward the area of lower concentration

Figure 4.11a

Active transport

Compounds move from area of low concentration toward area of higher concentration ATP (energy) is needed pump

ACTIVE MECHANISMS
Primary ionic transport

SECONDARY ACTIVE TRANSPORT

(SODIUM CO-TRANSPORT)
GUT
ATP AL NA ADP

NA

ACTIVE MECHANISMS CONT

BULK TRANSPORT
ENDOCYTOSIS
-PHAGOCYTOSIS -PINOCYTOSIS

EXOCYTOSIS

PATHOLOGIES

G-PROTEINS
GIANTISM or ACROMEGALY CHOLERA CHANNELS CYSTIC FIBROSIS

ATPase pumps

The most common: Na/K pumps reestablish membrane potential. Present in all cells. Two K+ ions are exchanged with 3 Na + ions

Phagocytosis

Receptor-mediated endocytosis
Cell receptors bind to a compound initiate endocytosis

Figure 4.21c

Hydrostatic Pressure

Pressure that a fluid exerts against structure enclosing it Increases with increased solute concentration Influences the osmotic movement of water

semipermeable membrane between two compartments

water molecule

protein molecu

2% sucrose solution

distilled water Hypotonic Conditions

10% sucrose solution Hypertonic Conditions

2% sucrose solution Isotonic Conditions

Hypotonic Solution membrane permeable to water but not to solutes

Hypertonic Solution

Red blood cell in hypertonic solution

Concentration of solute is higher outside cell Water leaves cell

Credit: Dr. David Phillips/Visuals Unlimited

Red blood cell in isotonic solution

Concentration of solute is equal inside cell and outside cell Little movement of water from osmosis Cell has normal shape

Credit: Dr. David Phillips/Visuals Unlimited

The Plasma Membrane

The Plasma Membrane

A Fluid Mosaic model

The membrane is made up of several components, including proteins, lipids, and carbohydrates that move in a lateral plane

The Plasma Membrane

Lipids

Phospholipids Cholesterol

Proteins

Integral Peripheral Glycoproteins Glycolipids

Carbohydrates

Transport

Membrane proteins are used for.

Enzymatic Activity

Signal Transduction

Cell-Cell Recognition

Intercellular Joining

HOW DO CELLS COMMUNICATE?

-Getting Information Across the Cell Membrane

1. Ionotropic
2. Metabotropic
3. Tyrosine Kinase

RECOGNITION PROTEINS

act as molecular fingerprints on the cell surface self recognition proteins identify cell type to other cells

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RECOGNITION PROTEINS

white blood cells are able to recognize self from non-self glycoproteins are extended into the extracellular fluid for easy access for recognition

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TYPES OF MEMBRANE PROTEINS

1) Channel Proteins 2) Active Transport Proteins 3) Receptor Proteins 4) Recognition Proteins

5) Adhesion Proteins

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ADHESION PROTEINS

connect cells together in a given tissue glycoproteins connect neighboring cells some may become cell junctions

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ADHESION PROTEINS

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ADHESION PROTEINS

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ROUTES ACROSS CELL MEMBRANES

1) Diffusion / Osmosis 2) Protein Mediated Diffusion

3) Endocytosis and Exocytosis

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EXOCYTOSIS AND ENDOCYTOSIS

move materials in bulk across cell membranes

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EXOCYTOSIS

cytoplasmic vesicles fuse to the cell membrane and contents are released to the outside of the cell

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ENDOCYTOSIS

1) Phagocytosis 2) Pinocytosis

region of the cell membrane sinks inward and balloons around substances, pinching itself off into a sealed vesicle which transports or stores the contents

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PHAGOCYTOSIS

cell eater

ex: amoeba, white blood cells (macrophage)

lobes of cytoplasm wrap around the trapped item and seal together newly formed vesicles fuse with lysosomes for digestion

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PINOCYTOSIS

cell drinking

ex: intestinal cell taking up liquid droplets

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T.K.

Tyrosine Kinase Mechanism

HOW DO CELLS COMMUNICATE?

-Getting Information Across the Cell Membrane

1. Ionotropic
2. Metabotropic 3. Tyrosine Kinase 4. Direct effect on genome

Lipid Soluble (often steroid)

Cell Communication

What does a talking cell say to a listening cell, and how does the latter respond?

Direct contact

Communication with messengers

Cell Communication

Direct contact can take two forms:

Cell Communication

Communication with messengers:

Local signaling Neuronal signaling

Long-distance signaling endocrine

paracrine
synaptic

Cell Communication

Discussion Question

Are nerve impulses an example of local signaling or long-distance communication?

Cell Communication

What happens when a cell encounters a signal?

Reception Transduction Response

Reception

The target cells detection of a signal molecule A chemical signal is detected when it binds to a receptor protein located at the cells surface or inside the cell

Transduction

The binding of the signal changes the receptor protein in some way, initiating the process of transduction Signal gets converted to a form that can bring about a specific cellular response Sometimes occurs as a single step, but usually multi-step Molecules in the pathway are called relay molecules

Response

Transduced signal triggers a specific cellular response Response can be:

Catalysis by an enzyme Rearrangement of the cytoskeleton Activation of genes

Overview

Activity

Problem-based learning: PBL You will be asked to research a particular disease that involves a scenario of an incorrect/damaged cell signaling pathway. By explaining whats wrong, you will learn whats normal