BIO (Book 1): Cell Membrane and Transport Across Membrane

Structure of membrane to its Function

Fluid Mosaic Model

• a ‘mosaic’ of proteins randomly distributed in or loosely attached to a fluid phospholipid bilayer

• a fluid phospholipid bilayer whereby phospholipids are free to move about laterally

Characteristics of the fluid mosaic model:

1. The fluid layer is asymmetrical.

• The two lipid layers (bilayer) may differ in composition and arrangement of proteins and lipids.

• The three major types of membrane lipids are phospholipids, cholesterol and glycolipids.

2. The phospholipid bilayer is fluid or mobile, i.e. lateral movement of phospholipids is possible.

3. The unit membrane is a dynamic structure, where the embedded proteins can float, some moving freely while others are fixed in positions by microfilaments on the cytoplasmic face.

4. Membranes are amphipathic.

• The hydrophilic phosphate head of the phospholipids face outwards into the aqueous environment both inside and outside of the cell;

• The hydrophobic hydrocarbon tails face inwards and create a hydrophobic core.

Membrane Fluidity

Bonds in the membrane:

• The membrane comprises of phospholipid molecules which are held together primarily by hydrophobic interactions between the hydrophobic fatty acid tails.

• As these are weak interactions, phospholipid molecules are free to move about laterally (slide left and right)

• It is quite rare for the molecules to flip transversely across the membrane, switching from one phosphoplipid layer to the other. This is because the hydrophilic part of the molecule must cross the hydrophobic core of the membrane in order to do so

The ability of the phospholipid molecules to move within the membrane accounts for the fluidity of the cell membrane.

Factors affecting Membrane Fluidity:

1. Temperature

2. Length of fatty acid chains

3. Degree of saturation of fatty acid chains

4. Amount of cholesterol

Factors affecting Membrane Fluidity → TEMPERATURE

Overall trend:

• As temperature decreases, membrane fluidity decreases, and vice versa.

• Membranes remain fluid as temperature decreases, until finally the phospholipids settle into a closely-packed arrangement and the membrane solidifies.

• This change of state (to semisolid) is known as the phase transition and the temperature at which it occurs is known as the phase transition temperature.

At LOW temperature:

• Kinetic energy of the hydrocarbon chains decreases

• Hydrocarbon chains are tightly packed

• This results in an increased hydrophobic interactions between phospholipid molecules and thus, their motion is restricted.

• The bilayer exists in a semisolid state, i.e. membrane is less fluid

At HIGH temperature:

• The kinetic energy and thus motion of the hydrocarbon chains increases

• This increase allows for increased lateral movements of individual molecules, flexing of the chains and transverse flipping,

• Thus overcoming hydrophobic interactions between phospholipids, resulting in increased space between adjacent phospholipid molecules.

• The bilayer exists in a fluid state, i.e. membrane is more fluid

Factors affecting Membrane Fluidity → LENGTH of fatty acid chains

Overall trend:

• As length of fatty acid chains increases, membrane fluidity decreases.

• In general, the longer the hydrocarbon chains, the higher the melting point (phase transition temperature) due to increased hydrophobic interactions between hydrocarbon chains.

Factors affecting Membrane Fluidity → Degree of saturation of fatty acid chains

General trend:

• As degree of saturation of fatty acid chains increases, membrane fluidity decreases and vice versa.

Saturated lipids: (C—C single bond)

• Have long, straight hydrocarbon chains

• This allows for close packing and thus enhances membrane solidification

Unsaturated lipids: (C—C double bond)

• Have kinks

• Kinks prevent the hydrocarbon chains from packing closely together thus enhances membrane fluidity

Mixtures of phospholipids broaden the temperature range of the transition phase considerably.

Factors affecting Membrane Fluidity → Amount of cholesterol

General trend:

• Cholesterol increases the stability and regulates the fluidity of membranes in animal cells.

Components of Cell Membrane

1. Phospholipids

2. Cholesterol

3. Proteins

4. Carbohydrates

Phospholipids

Each phospholipid molecule consists of:

1. a glycerol backbone (a three-carbon molecule) with three hydroxyl (-OH) groups

2. two fatty acid chains – contributing the hydrophobic hydrocarbon “tails”

3. a negatively charged phosphate group (PO₄^3-)

4. additional small, charged molecules which may be linked to the phosphate group

Phospholipid molecule is amphipathic:

• It has a hydrophobic “tail” and a hydrophilic “head”

• This property results in the formation of phospholipid bilayers in an aqueous environment (i.e. hydrophilic heads are exposed to water, while hydrophobic tails are sheltered from water)

Long hydrocarbon chains of fatty acids:

• Form an effective hydrophobic barrier against polar and charged solutes.

• As the fatty acid chains are much longer than the glycerol head, their length dictates the thickness of the membrane, which is about 8 nm.

Cholesterol

• Cholesterols are steroids

• Commonly found wedged between phospholipid molecules in the cell membranes of animal cells.

Functions:

1. Membrane stability:

• Cholesterol molecules are usually found in both layers of the cell membrane, intercalated into the lipid monolayers

• Its rigid steroid ring interferes with the motions of the hydrocarbon chains of phospholipids, thus enhancing the mechanical stability of the membrane.

2. Membrane fluidity:

• At HIGH temperature:

→ Cholesterol restrains the movements of phospholipids by interfering with the motions of the hydrocarbon chains,

→ Resulting in decreased membrane fluidity.

• At LOW temperature:

→ Cholesterol prevents the hydrocarbon chains from packing closely together

→ Thus decreasing the tendency of the membrane to freeze upon

→ Resulting in increased membrane fluidity.

In short, cholesterol has dual effects on the fluidity of the membrane; resisting changes in membrane fluidity that can be caused by changes in temperature, acting as a “temperature buffer” for the membrane.

3. Membrane permeability:

• Presence of cholesterol molecules decreases the permeability of a lipid bilayer to ions and small polar molecules.

• It does so by filling in spaces between hydrocarbon chains of phospholipids, thereby plugging transient gaps through which ions and small molecules might otherwise pass.

Proteins

Types of membrane proteins:

1. Integral (intrinsic) proteins

2. Peripheral (extrinsic) proteins

6 major types of function:

1. Anchorage

2. Transport

3. Enzymatic activity

4. Signal transduction

5. Cell-to-cell recognition

6. Intercellular joining

Functions of proteins → Anchorage

Anchoring proteins

• Attach the cell membrane to other substances

• Stabilise the position of the cell membrane

• Help maintain cell shape.

Anchoring proteins attached to the extracellular matrix can coordinate extracellular and intracellular changes

• On the cytoplasmic side: They are bound to microfilaments of the cytoskeleton.

• On the exterior side: They may attach the cell to fibres of the extracellular matrix.

Functions of proteins → Transport

Carrier proteins:

• Carrier proteins bind solutes and transport them across the membrane

• This transport process involves a conformational change of the protein when solute binding occurs, and a return to its original form when the solute is released.

• Energy in the form of ATP may or may not be required:

→ Facilitated diffusion: if solute moves down a concentration gradient (no energy external to the system is required)

→ Active transport: if solute moves against a concentration gradient (ATP is required)

Channel proteins:

• Some integral proteins contain a water-filled central pore, or hydrophilic channel

• This forms a passageway to permit the movement (down the concentration gradient) of water, ions and small hydrophilic solutes across the cell membrane.

• It participates in FACILITATED DIFFUSION (no ATP required)

• There are 2 major kinds of channels:

1. Leak channels

→ Permit movement of water at all times, e.g. aquaporins

→ Permit movement of ions at all times (though the rate may vary), e.g. Na+ or K+ leak channels

2. Gated channels

→ which can open or close to regulate ion passage

→ e.g. voltage-gated Na+ or K+ channels

Functions of proteins → Enzymatic activity

• These enzymes catalyse reactions in the extracellular fluid or within the cytosol, depending on the location of the active site

• In some instances, several enzymes can be grouped together to carry out sequential steps in a metabolic pathway.

Functions of proteins → Signal transduction

• These proteins have very specific 3D conformations, making them ideal as receptor molecules for chemical signalling between cells.

• Chemical signalling works by the binding of a ligand to the receptor protein which triggers changes in the cell

• Ligand → an ion, molecule, or functional group that binds to a receptor protein

• Cell membranes differ in the type and number of receptor proteins they contain. It is these differences that account for the differing sensitivities to hormones and neurotransmitters etc.

Functions of proteins → Cell-to-cell recognition

• Recognition proteins are usually glycoproteins (carbohydrate attached to proteins)

• There is a wide array of possible shapes to the carbohydrate side chains; hence each cell type has its own specific markers.

• This enables cells to recognise other cells, and provides a means for foreign markers to be recognised and attacked by the immune system.

Functions of proteins → Intercellular joining

• Membrane proteins of adjacent cells may adhere together in various kinds of intercellular junctions, such as gap junctions and tight junctions

Carbohydrates

• Membrane carbohydrates are usually short, branched chains of fewer than 15 sugar units

• Some of these are covalently bonded to polar ends of phospholipids molecules in the outer lipid layer, forming glycolipids

• Some are covalently bonded to membrane proteins, forming glycoproteins

Functions:

• The carbohydrate groups aid in maintaining the orientation of the glycoproteins and glycolipids within the membrane.

• As carbohydrates are highly hydrophilic, the glycolipids and glycoproteins are kept in contact with the external aqueous environment and are unlikely to rotate towards the interior to diffuse transversely.

• Due to the hydrophilic properties of carbohydrates, glycolipids and glycoproteins are important recognition components, such as those involved in:

1. Sorting of cells into tissues and organs in animal embryos

2. Binding extracellular signal molecules in antibody-antigen reactions

3. Intercellular adhesion to form tissues

4. Cell-to-cell recognition, that is the ability of a cell to distinguish one cell from another, e.g. the immune system identifies and acts upon foreign cells

Transport Across Membrane

Reasons for transport across membrane:

1. To maintain a suitable pH and ionic concentration within the cell for enzyme activity;

2. To obtain food supplies for energy and raw materials;

3. To excrete toxic substances

4. To secrete useful substances;

5. To generate the ionic gradients essential for nervous and muscular activity.

3 general types of transport:

1. Passive transport

2. Active transport

3. Bulk transport

Passive transport (diffusion)

Types of diffusion:

1. Simple diffusion

2. Facilitated diffusion

• Diffusion is the net movement of a substance (solute molecules) from a region of higher concentration to a region of lower concentration, that is, down a concentration gradient.

• Though diffusion is regarded as a form of passive transport, it is incorrect to assume that no energy is involved in the process.

• Instead, molecules have intrinsic kinetic (or thermal motion) energy, which is the tendency for them to spread out evenly into the available space. (but don’t require ATP)

• Diffusion continues until dynamic equilibrium is reached.

Passive transport → Simple Diffusion

Simple diffusion occurs for molecules that are able to cross the phospholipid bilayer directly without any need for the aid of channel or carrier protein

• Molecules that have a small molecular weight and / or are readily soluble in the lipid bilayer (hydrophobic molecules)

Diffusion can occur in either direction (i.e. from within the cell to outside the cell, or vice versa) depending on the concentration gradient.

Dynamic equilibrium is reached when concentrations of the diffusing substances are equal on both sides of the membrane. No net movement of substances then occurs

Energy from ATP is not needed.

Passive transport → Facilitated Diffusion

The principle of facilitated diffusion is similar to that of simple diffusion in that transport of substances occurs down a concentration gradient without the use of ATP until equilibrium is reached.

It is "facilitated" because a transport protein in the membrane is used to enhance / increase the rate of transport of the substance across the membrane.

Facilitated diffusion is used for larger, hydrophilic substances, such as glucose, amino acids and ions.

The involvement of the transport protein makes facilitated diffusion a type of channel-mediated or carrier-mediated transport, although it is passive.

The transport protein is specific to the substance being transported, i.e. it only transports that substance.