Membranes Overview

Question 1

Membranes: An overview

Answer 1

The plasma membrane defines the limits the cell
Membranes also define the limits of sub-cellular organelles such as the nucleus and mitochondria
Membranes regulate the transport of solutes as ot is semi-permeable.
Membranes detect and transmit electrical and chemical signals
Membranes provide surfaces upon which reactions can be conducted, such as the rough endoplasmic reticulum

Question 2

Biomembranes are composed of lipid bilayers

Answer 2

A major component of bio-membranes are lipids
The lipids found in cell membranes are amphiphatic because they contain a polar head unit as non-polar ‘tail’.
The hydrophilic heads and hydrophobic tails of lipids cause them spontaneously compose themselves into lipid bi-layers.
Due to this property, they can thermodynamically position themselves to suit an aquatic environment. So, they can spontaneously form membranes.

Question 3

Amphiphatic lipids can form bilayers

Answer 3

Heads face into the aqueous solution (either the outside or inside of the cell) while the tails stack upon themselves.
Two layers of ‘stacked’ lipids create the hydrophobic core of the lipid bilayer.

As the hydrophilic heads face outwards the aqueous solution and the body (tail) inwards away from the aqueous solution, a leaflet is formed.

Question 4

More about lipids

Answer 4

Examples of amphiphatic membrane lipids are phosphoglycerides, sphingolipids, (these are both types of phospholipids), galactolipid and cholesterol.
Lipids are not only important for membranes but are also important in energy storage and cell signalling.

Question 5

The classes of membrane lipids

Answer 5

Phospholipids:
Phosphoglycerides- when two fatty acids are attached to a glycerol, phosphate group and a head group.
Sphingolipids
Sphingosine is the base of the fatty acid attached. The sphingosine is normally attached to a phosphate group and a head group
Even though their bases are different- the phosphoglyceride’s base is glyceride and sphingolipids’s base is sphingosine; their structures look very similar.

Glycolipids: carbohydrate groups are attached to the amphiphatic lipid. These are particularly in nerve cells. These generally face outwards

The inside and outer leaflet of the membrane do not have to be the same composition- in actuality, they are very different in composition. 
So, glycolipids are generally found in the outer leaflet of the plasma membrane and glycolipids have specialist functions. A class of them especially is very important in nerve transmission.
Examples of glycolipids are cerebrosides and gangliosides and particularly found on the outer leaflet of nerve cells.

Cholesterol: cholesterol is a steroid. They look very different because they are based around fatty acids. Cholesterol has got a completely different structure to phospholipids and glycolipids, but when looked 3 dimensionally, it looks similar to these structures.
Cholesterols have a small polar head and a large hydrophobic body that can pack very nicely against the phospholipids.
Sterol-based cholesterol is really important in what is called buffering the membrane- ensuring that the membrane doesn’t get too rigid or too sloppy. So, sterols are very important in maintaining the fluidity of the membrane.
Its polar head is OH.

Question 6

Different membranes have different lipid compositions

Answer 6

Membranes fulfil many different roles in a cell therefore their properties must vary.

Varying the lipid composition varies the physical properties of the membrane. Each leaflet is different to the other; different composition so different physical properties.

Fluidity of the membrane is dependent on:
The ratio of saturated to unsaturated fatty acids
The length of the fatty acid tails- there is a lot of support from the Van der Waal forces that occur when the fatty acids pack against each other. Long tails, more Van der Waals, less fluidity. Vice versa for short tails

Saturated fatty acids pack much better than unsaturated fatty acids; unsaturated fatty acids can cause kinks in the tail which disrupts the packing of he hydrophobic tails.
Very fluid- not crystalline
Not fluid- more crystalline

Saturated fatty acids tends to make it less fluid; if it goes far enough, it becomes a crystaline structure.

So if you want a less fluid lipid, more of the fatty acids should be saturated and the length of these should be long.
The conditions also affect the fluidity of these fatty acids. The warmer the condition, the more fluid the fatty acids are.
We want a good balance of fluidity and crystalline so it is neither too fluid or too crystalline. Cholesterol comes here.

The percentage of cholesterol can affect the fluidity of the membrane
Cholesterol can ‘buffer’ the fluidity
Stops in becoming too fluid
Stops it becoming too crystaline

The head to tail size ratio can influence membrane curving
By changing the ratios of the head to the tail, you can curve the membrane
For example, if the ratios are proportionate the head and the tail, he membrane is straight.
If the ratio of the tail is larger the ratio of the head, then the membrane curves.

Question 7

The lipid bilayer is fluid (the fluid mosaic model)

Answer 7

Membrane lipids can move laterally in their lipid layer, but rarely flip into the opposing layer of the bilayer.
The long chain fatty acids of the phospholipids pack against each other stabilized by van der waals forces
The longer the chain, and hence the greater the van der waals forces, the less freedom (fluidity) the lipid will have in the membrane

Within a leaflet, lipid can move laterally in their layer but cannot flip into the opposite layer within the bilayer. There is energetic barriers against this happening.
It can happen at a very low current but it is rare though.

Question 8

Flippases

Answer 8

The two layers of the lipid bilayer are sometimes referred to as leaflets
These leaflets often have different composition of lipids
To move from one leaflet to another is a much slower process than lateral movement within the leaflet.
The process is facilitated by integral membrane proteins called flippases.

When you make the membrane, you got to ensure the lipid layers have different compositions- the outside composition of the lipid biomembrane is different to the inside composition of the lipid biomembrane.
This enzyme flips them where they want to be. Helps to maintain the asymmetry between the outer and inner.
Flippases helps to flip the lipids back which spontaneously flipped at a low current to the opposite leaflet.
This is a protein embedded within the lipid bilayer. It can take a specific lipid type and flip it between the leaflets.

Question 9

Proteins’ float in the lipid bilayer

Answer 9

A variety of proteins float in the lipid bilayer. They represent the mosaic part of the fluid mosaic model of membrane structure.
The proteins associated with the lipid bilayer can be broken down into 3 main groups
Lipids anchored membrane proteins
Peripheral membrane proteins
Integral membrane proteins- possible because their mid part is hydrophobic and their ends are hydrophilic

Alpha helix is a protein structure which is very versatile
Many proteins that span the lipid bilayer compose of alpha helices
because it is very easy to compose an alpha helix- with hydrophobic amino acids residue from which its composed poking out.

Peripheral proteins- loose attached to the leaflet-non covalently attached to the leaflet (may even be another protein which is embedded in the bilayer);so very easy to get off the bilayer.

Lipid anchored membrane proteins- these are chemically covalently attached to the lipids and very hard to get off

The membrane needs a variety of proteins e.g transmembrane receptors.

Question 10

The layers of the lipid bilayer are asymmetric

Answer 10

The layers can be asymmetric both in the composition of the lipids and proteins because one faces inwards and the other faces outwards
The inner leaflet is composed of intracellular proteins whereas the outer leaflet has extracellular proteins

Some proteins are mobile in their layer, while others are locked in place by anchoring to either the cytoskeleton (inside) of the extracellular matrix (outside).
The extracellular (ECM) matrix lies outside the plasma membrane of multicellular eukaryotes
The outer leaflet engages with the ECM and the inner leaflet engages with the cytoskeleton of the cell.
The cytoskeleton is an array of filaments beneath the plasma membrane that provides support to the cell.

Question 11

The cell wall

Answer 11

The cell wall is a rigid structure surrounding plant (and some fungi) cells
It is composed of cellulose microfibrils embedded in pectin and hemicellulose
The plasma membrane is associated with the cell wall
The cell wall provides support for the cell wall and helps prevent it bursting in a hypertonic solution

Question 12

Getting across the barrier

Answer 12

Membranes define a barrier between an inside and an outside in a cell the inside must interact with the outside
Examples of the selective permeability of membranes include:
Bulk transfer by endo and exocytosis
Secreting and importing proteins
Solute molecules such as ions e.g Na+, K+, Cl- (important in nerve function) there are protein structures for these ions that allow them to pass through however they are impermeable to the membrane.
Solute molecules such as metabolites e.g sugars, amino acids

Question 13

Ways of getting across the barrier

Answer 13

Simple diffusion e.g oxygen
Diffusion can only work down a concentration gradient towards equilibrium:
High-> Low
Small uncharged polar molecules can diffuse across the membrane best
It is energetically more favourable by the universe for a molecule/ particle to drift from a high concentration to a low concentration

Question 14

Osmosis: a special case of simple diffusion

Answer 14

Diffusion of water is known as osmosis
The plasma membrane is highly permeable to water because of protein structures called aquaporins- other water is semi-permeable to the membrane
In relation to the cell interior solutions can be:
Hypotonic- when the solution is less concentrated
Isotonic- when the solutions are equally concentrated
Hypertonic- when the solution is more concentrated

Question 15

Facilitated diffusion

Answer 15

Still diffuses down the gradient but larger and/or polar molecules are helped
Important for ion transport; ions which cannot get through the membrane as its impermeable to it.
Facilitated diffusion can be sub-divided into two types, requiring two different types of integral membrane protein:
(Both of these type of proteins are integral transmembrane protein complexes which allow molecules to pass through the membrane that otherwise won’t be able to get through- but it is still going from a high region to a low region) doesn’t require any input from the cell- its spontaneous.
Carrier proteins: binding of solute causes a conformational change in the membrane molecule which transports the solute across the membrane
They tend to be specific for specific molecule type. Hide the molecule from the membrane’s hydrophobic core and pass it across the membrane outside.
Channel proteins:
Form a hydrophilic passage through the membrane

Question 16

Active transport

Answer 16

Active transport can move molecules against a concentration gradient
Life is constantly out of thermodynamic equilibrium.
Active transport can be sub-divided into classes
Direct active transport:
The energy required to move against the gradient comes from ATP hydrolysis
Hydrolysis of glucose can be used to stick a phosphate group to ADP to form ATP. This stored energy can be expended by hydrolysing the terminal phosphate off the ATP.
Indirect active transport:
The energy required to move against the gradient comes from co-transport of a solute favourably down its gradient.
E.g diffusion.
The energy release from moving molecules from a high to low concentration can be used to move molecules from low to high.
The substrate (that passively moves through the membrane; goes down its gradient), powers the other substrate that moves against its concentration gradient. So, extra energy isn’t needed to move the substrate (that is moving against its concentration gradient) across the membrane. So, these substrates co-transport across the membrane. So, this energy released by this whole co-transport is used for another direct transport.

Question 17

Differences in cytosolic ion concentrations

Answer 17

The cytosolic pH is maintained at around 7.2 by regulating hydrogen ion concentration
In general the K+ concentration is higher intracellular than extracellular
In general the Na+ concentration is lower intracellular than extracellular

This is maintained by an ion pump.

Question 18

Direct ATP powered pumps maintain an ionic gradient across the membrane

Answer 18

The ionic concentration of inside cells is different to that outside the cell
The differences in ion concentration between the inside and outside is maintained by ATP powered ion pumps and ion channels
The differences in ion concentration means there is electrical potential of about 70mV across the membrane; there is a charge separation between the interior and the exterior (across the membrane) of about 70mV. Every cell has a resting potential that is 70mV.

Question 19

Synthesis of the membrane

Answer 19

Cell synthesise new membranes by the expansion of existing membranes
You cannot keep synthesising an amphiphatic molecule because if you do so, the hydrophobic tail will keep on getting longer and longer and less and less soluble until this will form an aggregate- a clump up.
Lipid precursers are synthesised in the cytosol
Synthesis continues in the SER (after synthesis finishes, they bud off to where ever they are needed).
Many membrane lipids are distributed to their target membranes by vesicles.
Some membranes grow receive membrane lipids by a vesicle independent mechanism

Question 20

What is cell signalling

Answer 20

It describes communication between cells
It usually involves a chemical messenger (signal/ligand), released by the signalling cell
The signal is detected by the responding cell (receptor)
Signal detection triggers intracellular reactions that influence the behaviour of the responding cell; causes a change in the behaviour of the responding cell

Question 21

The tasks of cell communication

Answer 21

Signal release from a source cell and it interacts with a receiving cell; the receiving cell generally activates a receptor. The receptor will ultimately lead the change in transcription within the cell. The signal transduction pathway will change which genes are on and which genes are off.
-synthesis and excretion of the signalling molecule
Signal detection
-interaction of signal and receptor
Signal transduction
-translation of detection to changes in cell physiology or gene expression

Question 22

Signals

Answer 22

Paracrine
-acts on local set of cells; the signal diffuses away from the source cell. As this relies on diffusion, the signal tends to not go tremendously far distance.
Autocrine
-acts on the secreting cell; also diffuses away from the secreting cell so the signal doesn’t travel far distant from the source cell. The signal can affect the secreting cells in autocrine.
Endocrine
-long range signals moving through the blood stream; signals moved through the blood stream and so can affect a much wider community of cells

Question 23

Signalling and control of gene expression

Answer 23

Cell-cell signalling can change the repertoire of transcription factors in the responding cell, resulting in different gene expression

Question 24

How does the signal enter the cell

Answer 24

The signals can be an organic molecule or a protein. These signals are diffused or carried to other cells. These cells will respond depending on what signal is send to them after the correct receptors on the cells receive them.
Two strategies:
1. The signal can pass through (diffuse through) the plasma membrane if its a hydrophobic molecule; received by nuclear receptors which remain in the cytosol of the cell (so inside the cell). These nuclear receptors are also called transcription factors because these will ultimately change the behaviour of the responding cell by determining what genes are on or off within the nucleus.
2. These type of receptors are transmembrane receptors. Some stick out of the cell and some stick inside the cell and are connected by a bit of protein embedded in the membrane. These receptors receive these signals on the outer part and then changes their structure which activates the inner part of the receptor. This then ultimately leads to signal transduction pathway which then will affect which genes are on or off in the cell.
The signal can activate a membrane receptor. Examples of these are:
- G protein linked receptors
- serine/threonine kinase receptors

Question 25

Nuclear receptors

Answer 25

The signals are steroids or retinoids
These signals can pass through the plasma membrane
In the cytoplasm they encounter nuclear receptors
This complex then enters the nucleus to activate genes

Once the receptor receives its signal, it moves from the cytoplasm to the nucleus. Once it is in the nucleus, it can change which genes are on or off because nuclear receptors are also transcription factors. Transcription factors are proteins which regulate which genes get turned on and which genes get turned off.

Question 26

Signalling through nuclear receptors

Answer 26

Nuclear receptors like the glucocorticoid receptor are cytoplasmic proteins

• in their inactive form, they are bound to Hsp chaperones
• ligand binding releases the Hsp
• the receptor-ligand complex moves to the nucleus to activate the transcription of target genes

Question 27

G-protein linked receptors

Answer 27

Transmembrane receptors are linked to a G-protein; the inner part of the receptor is linked to a G-protein.
G-protein is composed of G-alpha, G-beta and G-gamma.
The binding of the extracellular ligand to the outer part of the transmembrane causes conformational change; it affects the internal trimeric G-protein complex (G-alpha, G-beta and G-gamma). G-alpha releases GDP upon binding of the ligand and takes up GTP
Upon ligand binding the G protein releases GDP and takes up GTP. While it does so, G-beta and G-gamma are left behind to become functional. So, they activate other proteins. G-alpha hydrolyses GTP to GDP. Now, G-alpha returns to G-beta and G-gamma forming its trimeric complex and so inactivating G-beta and G-alpha and G-beta. Upon the ligand binding to the receptor, the G- trimeric protein complex is activated and will activated as long as it takes for G-alpha to hydrolyse GTP to GDP.

Galpha dissociates from G beta gamma and activates downstream ‘second messengers’ (e.g cAMP)
GTP is hydrolysed to GDP and G alpha reassociates with G beta gamma

Question 28

Serine/ theronine Kinase receptors

Answer 28

Transmembrane receptors that bind that TGF-beta family of signals- these signals are very important in early development.
The binding of the TGF-beta to the receptor, causes the receptors to cluster on the surface where they can phosphorylate each other (autophosphorylate (phosphorylate itself)). This phosphorylation activates a downstream of pathway, SMAD. SMAD can interact with a protein called co-smad. Then co-smad enter the nucleus and changes which genes are on and off.
Ligand brings type I and type II receptors
II phosphorylates I
Smads become phosphorylated and move into the nucleus to act as transcription factors

Question 29

What is an endomembrane system

Answer 29

The little sacs of membrane (Golgi body) travel between different organelles and form this

Question 30

What defines a lipid

Answer 30

Something that is not soluble in water because they are not polar or charged.
They are uncharged

Question 31

What is a leaflet

Answer 31

One half of a lipid bilayer

Question 32

How many leaflets do phospholipid bilayer and liposome have

Answer 32

2

Question 33

What can liposomes do

Answer 33

Liposomes have a cavity in the middle where it is aqueous. So, we can out water in that cavity as well as other molecules.
Liposomes are sometimes used as delivery mechanism. When two membranes meet, they merge. So, for example, if the liposome was to touch the phospholipid bilayer of the plasma membrane, it would merge. So, its contents in the cavity would be delivered into the cell.

Question 34

Blood grouping

Answer 34

Glycolipids are responsible for this.

Question 35

The three types of filaments

Answer 35

The three types of proteins that form the long fibrous structures of cytoskeleton:
Microtubules
Microfilaments/ actin filaments
Intermediate filaments

They form long, fibrous multimeric structures which are constantly being taken apart and rebuild very easily because they are composed by monomers that can be polymerised into long structure.
The general theme for cytoskeleton is that they are long fibrous structures composed of smaller globular structures usually; which can be stuck together to form very long and strong fibres.

Question 36

Blood groups

Answer 36

Blood group antigens are either sugars or proteins, and they are attached to various components in the red blood cell membrane.
They are produced by a series of reactions in which enzymes catalyse the transfer of sugar units. A person’s DNA determines the type of enzymes they have, and, therefore, the type of sugar antigens that end up on their red blood cells.

Question 37

Definition of multimeric

Answer 37

Describing a protein that has multiple polypeptide chains.

Question 38

How many classes of each respective filaments are there

Answer 38

Microtubules- only one class
Microfilaments- only one class

Intermediate filament- many including lamins

Question 39

What can pass through the selectively semi permeable membrane

Answer 39

No everything can pass through but certain things can be allowed to pass through
Small uncharged molecules such as carbon dioxide, nitrogen gas and oxygen gas can pass through the membrane through diffusion
However, small charged molecules really struggle to pass through due to the hydrophobic barrier
A lipid bilayer is partially permeable to water however in cells, in plasma membrane, there are special structures called aqua-porins. These act as a passage for water.
Large molecules such as glucose and fructose can get through because they are too big to get through
Charged polar molecules such as ATP, amino acids, proteins and nucleic acids cannot pass through
However, there are protein structures in the lipid bilayer which let molecules through which otherwise wouldn’t be able to pass through

Question 40

What happens in a hypertonic, hypotonic and isotonic solution

Answer 40

Hypertonic solution- when the animal cell is placed in a more concentrated solution, the animal cell would shrivel and a plant cell would become plasmolysed.
In an isotonic solution- the animal and plant cell would stay the same since both solutions inside and out of the cell have the same concentration
The plant cell cell would become flaccid
Hypotonic solution- when an animal cell is put in a hypotonic solution (the surrounding solution is less concentrated), the animal cell would become lysed as water molecules would move in.
A plant cell would become turgid.

Question 41

What is symport and antiport (indirect active transport)

Answer 41

Indirect transport can be broken down into symport and antiport.
Symport meaning the two substrates that co-transport (one going down its concentration gradient and the other substrate moving against its concentration gradient) move in the same direction- go from one side of the membrane to the other together.
Antiport- the substrates that co-transport move in opposite directions. So, one moves from one side of the membrane to the other whilst the other substrate moves in the opposite direction.

Question 42

Exo and endocytosis

Answer 42

Exo- A vesicle containing contents needed for signalling for example can fuse with the plasma membrane and release the contents out to the exterior side

Endocytosis- the plasma membrane invaginating whilst grabbing chunks of exterior environment. Then pinch off a vesicle ball and can be taken into the interior of the cell

Question 43

How do you transport newly synthesised phospholipids from teh SER to its target membrane

Answer 43

Two ways
Either a bit of the SER membrane buds off carrying the phospholipids to its target membrane or this section of newly synthesised phospholipids are transported through a carrier protein to its target membrane.

Question 44

What is a ligand

Answer 44

A small molecule/ object that binds to a receptor

A ligand and a signal are interchangeable

Question 45

What is a signal transduction pathway

Answer 45

The series of intracellular reactions that occur within the responding cell and are triggered by signal detection by a receptor.
These reactions affect the behaviour of the responding cell.

Question 46

Competence for a signal

Answer 46

A cell will only respond to a secreted signal if it has appropriate receptor.
In paracrine, the secreting cell doesn’t have the receptor for the secreted signal but in autocrine, the secreting cell does.
So, the secreted signal affects the secreting cell in autocrine. In other aspects, paracrine and autocrine are very similar.

Question 47

How does the whole signalling process look like

Answer 47

An extracellular signal molecule attaches to its complementary receptor protein. This signal detection activates a protein which then activates another protein and this causes the activation of another protein. So, the activation of these proteins one by one, starting from the signal detection by the receptor, is called signal transduction pathway and these proteins that are activated one after the one are called intracellular signaling proteins. The activation of the first intracellular protein affects the activation of the next one in line and so on.
The signal transduction pathway can cause in many changes- one of which being gene expression being altered. So, altering which genes are on or off(in the receiving cell), meaning that the behaviour, shape and morphology of the cell will change.
In other words, signalling allows altering of the transcriptome.

Question 48

What is a transcriptome

Answer 48

All the genes that are activate and are producing RNA.

Question 49

Morphogenetic gradients

Answer 49

How does an embryo (a ball of unspecialised cells) know how to differentiate and grow into specialised cells
The answer is cell signalling. Some cells within the ball of cells (embryo) are secreting signals and that signal induces other cells to become differentiated cell types.
Some morphogenetic gradient can affect cells differently depending in the dosage.
Signals diffuse away from the secreting cells. Since, these signals are diffusing, near the secreting cells, there is a high concentration of the signal. Consequently, further away from the secreting cells, there is a low concentration of the signal.
So, the cells near the secreting cells, will respond accordingly to the signal. However, the cells further away from the secreting cells will receive lower concentration of the signal so they will respond in a different way- because they receive the signal but in lower dosages than the cells nearby the secreting cells.
So a morphological gradient is the varying responses of the cells to the signal due to the varying dosages they receive.

Question 50

What does G-gamma and G-beta do when G-alpha has run off with GTP.

Answer 50

In this specific example, these parts activate cAMP. cAMP is derived from ATP.
cAMP is a very important, general second messenger.
Once the signal has been received from outside the cell, cAMP can be used as an internal messenger within the cell.

G-beta and G-gamma make a lot of cAMP. cAMP activates a protein called Protein Kinase A. Kinases can phosphorylate other proteins- this is a type of post-translational modification (changes made to a protein that has already been synthesised). It adds a phosphate group to the protein CREB- so it activates the protein CREB as an transcription factor and this changes which genes are on and off.