1. 1.3 Membrane Structure
Edited By Eran Earland
Essential idea: The structure of biological membranes makes them fluid and dynamic.
Above are models of a plasma membrane showing how it's fluidity allows lipid soluble molecules to move directly through the membrane.
Chris Paine and Bioninja.com

2. Understandings, Applications and Skills
Statement
Guidance
1.3.U1
Phospholipids form bilayers in water due to the amphipathic properties of phospholipid molecules.
Amphipathic phospholipids have hydrophilic and hydrophobic properties.
1.3.U2
Membrane proteins are diverse in terms of structure, position in the membrane and function.
1.3.U3
Cholesterol is a component of animal cell membranes.
1.3.A1
Cholesterol in mammalian membranes reduces membrane fluidity and permeability to some solutes.
1.3.S1
Drawing of the fluid mosaic model.
Drawings of the fluid mosaic model of membrane structure can be two dimensional rather than three dimensional. Individual phospholipid molecules should be shown using the symbol of a circle with two parallel lines attached. A range of membrane proteins should be shown including glycoproteins.
1.3.S2
Analysis of evidence from electron microscopy that led to the proposal of the Davson-Danielli model.
1.3.S3
Analysis of the falsification of the Davson-Danielli model that led to the Singer-Nicolson model.

3. What happens when you put a drop of oil in water?
1.3.U1 Phospholipids form bilayers in water due to the amphipathic properties of phospholipid molecules.
What happens when you put a drop
of oil in
water?

4. The Oil droplet stays together and makes a perfect circular shape.
1.3.U1 Phospholipids form bilayers in water due to the amphipathic properties of phospholipid molecules.
The Oil droplet stays together and makes a perfect circular shape.
The oil molecules are
Hydrophobic
Oil Molecules are non-polar and water
molecules are polar.
See 3.1.5

5. Link to Topic 2.2 Water
Understanding: 2.2 U1 - Water molecules are polar and hydrogen bonds form between them
Water is made up of two hydrogen atoms covalently bonded to an oxygen atom (molecular formula = H2O)
While this covalent bonding involves the sharing of electrons, they are not shared equally between the atoms
Oxygen (due to having a higher electronegativity) attracts the electrons more strongly
The shared electrons orbit closer to the oxygen atom than the hydrogen atoms resulting in polarity

6. The head is hydrophillic (attracted to water)
1.3.U1 Phospholipids form bilayers in water due to the amphipathic properties of phospholipid molecules.
Phospholipid molecules have a polar (charged) phosphate head and long non-polar lipid tails
The head is hydrophillic (attracted to water)
The tails are hydrophobic (repelled by water)
When drawing a diagram of a phospholipid this is a good example which shows all the key features

7. 1.3.U1 Phospholipids form bilayers in water due to the amphipathic properties of phospholipid molecules.
When put into water, an emergent property is that phospholipids will self-organise to keep their heads ‘wet’ and their tails ‘dry’
micelle
liposome
Arrangement in Membranes:
Phospholipids spontaneously arrange into a bilayer
The hydrophobic tail regions face inwards and are shielded from the surrounding polar fluids, while the two hydrophilic head regions associate with the cytosolic and extracellular fluids respectively

8. 1.3.U1 Phospholipids form bilayers in water due to the amphipathic properties of phospholipid molecules.
In this 3D representation you can see that a phospholipid bilayer is one way that the tails can be removed from the water.
Phospholipid molecules can flow past each other laterally but can’t move vertically

9. Properties of the Phospholipid Bilayer:
1.3.U1 Phospholipids form bilayers in water due to the amphipathic properties of phospholipid molecules.
Properties of the Phospholipid Bilayer:
The bilayer is held together by weak hydrophobic interactions between the tails
Hydrophilic / hydrophobic layers restrict the passage of many substances
Individual phospholipids can move within the bilayer, allowing for membrane fluidity and flexibility
This fluidity allows for the spontaneous breaking and reforming of membranes (endocytosis / exocytosis)

10. The plasma membrane is not just made of phospholipids
1.3.U1 Phospholipids form bilayers in water due to the amphipathic properties of phospholipid molecules.
But wait! there’s more!
The plasma membrane is not just made of phospholipids

11. 1.3.U2 Membrane proteins are diverse in terms of structure, position in the membrane and function.
Phospholipid bilayers are embedded with proteins, which may be either permanently or temporarily attached to the membrane
Integral proteins are permanently attached to the membrane and are typically transmembrane (they span across the bilayer)
Peripheral proteins are temporarily attached by non-covalent interactions and associate with one surface of the membrane

12. Connections to Topic 2. 4 – Proteins http://ib. bioninja. com
Structure of Membrane Proteins
The amino acids of a membrane protein are localized according to polarity:
Non-polar (hydrophobic) amino acids associate directly with the lipid bilayer 
Polar (hydrophilic) amino acids are located internally and face aqueous solutions

13. Connections to Topic 2. 4 – Proteins http://ib. bioninja. com
Structure of Membrane Proteins
Transmembrane proteins typically adopt one of two tertiary structures: 
Single helices / helical bundles 
Beta barrels (common in channel proteins)

14. Functions of Membrane Proteins
1.3.U2 Membrane proteins are diverse in terms of structure, position in the membrane and function.
Functions of Membrane Proteins
Membrane proteins can serve a variety of key functions:
Junctions – Serve to connect and join two cells together
Enzymes – Fixing to membranes localizes metabolic pathways
Transport – Responsible for facilitated diffusion and active transport
Recognition – May function as markers for cellular identification
Anchorage – Attachment points for cytoskeleton and extracellular matrix
Transduction – Function as receptors for peptide hormones
Mnemonic: Jet Rat

15. Cell Membrane Protein Functions

16. 1.3.U2 Membrane proteins are diverse in terms of structure, position in the membrane and function.
Glycoproteins:
Are proteins with an oligosaccaride (oligo = few, saccharide = sugar) chain attached.
They are important for cell recognition by the immune system and as hormone receptors

17. Transport: Protein channels (facilitated) and protein pumps (active)
1.3.U2 Membrane proteins are diverse in terms of structure, position in the membrane and function.
Transport: Protein channels (facilitated) and protein pumps (active)
Receptors: Peptide-based hormones (insulin, glucagon, etc.)
Anchorage: Cytoskeleton attachments and extracellular matrix
Cell recognition: MHC proteins and antigens
Intercellular joinings: Tight junctions and plasmodesmata
Enzymatic activity: Metabolic pathways (e.g. electron transport chain)

18. 1.3.U3 Cholesterol is a component of animal cell membranes.
Cholesterol: (It’s not all bad!)
It makes the phospholipids pack more tightly and regulates the fluidity and flexibility of the membrane.
Bad analogy: imagine a room full of people wearing fluffy jumpers (sweaters).
It is crowded but they can slip past each other easily enough.
Now sprinkle the crowd with people wearing Velcro™ suits…

19. Cholesterol is a component of animal cell membranes, where it functions to maintain integrity and mechanical stability
It is absent in plant cells, as these plasma membranes are surrounded and supported by a rigid cell wall made of cellulose
cholesterol molecule
Cholesterol is an amphipathic molecule (like phospholipids), meaning it has both hydrophilic and hydrophobic regions
Cholesterol’s hydroxyl (-OH) group is hydrophilic and aligns towards the phosphate heads of phospholipids
The remainder of the molecule (steroid ring and hydrocarbon tail) is hydrophobic and associates with the phospholipid tails

20. 1.3.U3 Cholesterol is a component of animal cell membranes.
Hydroxyl group makes the head polar and hydrophilic - attracted to the phosphate heads on the periphery of the membrane.
Carbon rings – it’s not classed as a fat or an oil, cholesterol is a steroid
Non-polar (hydrophobic) tail –attracted to the hydrophobic tails of phospholipids in the centre of the membrane

21. 1.3.A1 Cholesterol in mammalian membranes reduces membrane fluidity and permeability to some solutes.
Membrane fluidity
The hydrophobic hydrocarbon tails usually behave as a liquid. Hydrophilic phosphate heads act more like a solid.
Though it is difficult to determine whether the membrane is truly either a solid or liquid it can definitely be said to be fluid.
It is important to regulate the degree of fluidity:
Membranes need to be fluid enough that the cell can move
Membranes need to be fluid enough that the required substances can move across the membrane
If too fluid however the membrane could not effectively restrict the movement of substances across itself

22. Cholesterol’s role in membrane fluidity
1.3.A1 Cholesterol in mammalian membranes reduces membrane fluidity and permeability to some solutes.
Cholesterol’s role in membrane fluidity
The presence of cholesterol in the membrane restricts the movement of phospholipids and other molecules – this reduces membrane fluidity. 1.
The presence of cholesterol disrupts the regular packing of the of the hydrocarbon tails of phospholipid molecules - this is increases the flexibility as it prevents the tails from crystallising and hence behaving like a solid. 2.
Cholesterol also reduces the permeability to hydrophilic/water soluble molecules and ions such as sodium and hydrogen. 3.

23. Setting it Straight Fluidity vs Flexibility
Fluid means that the embedded proteins or carbohydrates attached to the cell membrane have the ability to move around within the membrane.
Flexible means its lipid bilayers would be able to bend easily
Fluidity does not mean flexible.
Cholesterol reduces fluidity (ability of proteins etc. to move within the membrane) and permeability, but increases the flexibility (lipids hold to gether more so can flex, but this means “things” can’t move through or within those layers as easily)

24. 1.3.S1 Drawing of the fluid mosaic model.
Use the tutorials to learn and review membrane structure

25. 1.3.S1 Drawing of the fluid mosaic model.

26. 1.3.S1 Drawing of the fluid mosaic model.
Good use of space
Clear strong lines
Label lines are straight
Labels clearly written
(Scale bar if appropriate)
Lines touch the labeled structure
No unnecessary shading or colouring
Reminder of features that make good diagrams:

27. 1.3.S2 Analysis of evidence from electron microscopy that led to the proposal of the Davson-Danielli model.
The fluid-mosaic model was not the first scientifically accepted paradigm to describe membrane structure
The first model that attempted to describe the position of proteins within the bilayer was proposed by Hugh Davson and James Danielli in 1935
When viewed under a transmission electron microscope, membranes exhibit a characteristic 'trilaminar’ appearance
Trilaminar = 3 layers (two dark outer layers and a lighter inner region)

28. 1.3.S2 Analysis of evidence from electron microscopy that led to the proposal of the Davson-Danielli model.
Danielli and Davson proposed a model whereby two layers of protein flanked a central phospholipid bilayer
The model was described as a 'lipo-protein sandwich’, as the lipid layer was sandwiched between two protein layers
The dark segments seen under electron microscope were identified (wrongly) as representing the two protein layers

29. 1.3.S3 Analysis of the falsification of the Davson-Danielli model that led to the Singer-Nicolson model.
There were a number of problems with the lipo-protein sandwich model proposed by Davson and Danielli:
It assumed all membranes were of a uniform thickness and would have a constant lipid-protein ratio 
It assumed all membranes would have symmetrical internal and external surfaces (i.e. not bifacial)
It did not account for the permeability of certain substances (did not recognise the need for hydrophilic pores) 
The temperatures at which membranes solidified did not correlate with those expected under the proposed model 

30. Falsification Evidence:
1.3.S3 Analysis of the falsification of the Davson-Danielli model that led to the Singer-Nicolson model.
Falsification Evidence:
Membrane proteins were discovered to be insoluble in water indicating hydrophobic surfaces) and varied in size
Such proteins would not be able to form a uniform and continuous layer around the outer surface of a membrane
Fluorescent antibody tagging of membrane proteins showed they were mobile and not fixed in place
Membrane proteins from two different cells were tagged with red and green fluorescent markers respectively
When the two cells were fused, the markers became mixed throughout the membrane of the fused cell
This demonstrated that the membrane proteins could move and did not form a static layer (as per Davson-Danielli)
Freeze fracturing was used to split open the membrane and revealed irregular rough surfaces within the membrane 
These rough surfaces were interpreted as being transmembrane proteins, demonstrating that proteins were not solely localised to the outside of the membrane structure

31. 1.3.S3 Analysis of the falsification of the Davson-Danielli model that led to the Singer-Nicolson model.
New Model:
In light of these limitations, a new model was proposed by Seymour Singer and Garth Nicolson in 1972
According to this model, proteins were embedded within the lipid bilayer rather than existing as separate layers
This model, known as the fluid-mosaic model, remains the model preferred by scientists today (with refinements)

32. 1.3.S3 Analysis of the falsification of the Davson-Danielli model that led to the Singer-Nicolson model.
Our current model of the cell membrane is called the Singer-Nicholson fluid mosaic model
Key features:
Phospholipid molecules form a bilayer - phospholipids are fluid and move laterally
Peripheral proteins are bound to either the inner or outer surface of the membrane
Integral proteins - permeate the surface of the membrane
The membrane is a fluid mosaic of phospholipids and proteins
Proteins can move laterally along membrane

33. 1.3.S3 Analysis of the falsification of the Davson-Danielli model that led to the Singer-Nicolson model.
Our current model of the cell membrane is called the Singer-Nicholson fluid mosaic model
There is strong evidence for this model:
Biochemical techniques
Membrane proteins were found to be very varied in size and globular in shape
Such proteins would be unable to form continuous layers on the periphery of the membrane.
The membrane proteins had hydrophobic regions and therefore would embed in the membrane not layer the outside

34. Fluorescent antibody tagging
1.3.S3 Analysis of the falsification of the Davson-Danielli model that led to the Singer-Nicolson model.
Our current model of the cell membrane is called the Singer-Nicholson fluid mosaic model
There is strong evidence for this model:
Fluorescent antibody tagging
red or green fluorescent markers attached to antibodies which would bind to membrane proteins
The membrane proteins of some cells were tagged with red markers and other cells with green markers.
Within 40 minutes the red and green markers were mixed throughout the membrane of the fused cell.
This showed that membrane proteins are free to move within the membrane rather than being fixed in a peripheral layer.
The cells were fused together.

35. This model was first proposed in by Singer-Nicolson in 1972
1.3.S3 Analysis of the falsification of the Davson-Danielli model that led to the Singer-Nicolson model.
Our current model of the cell membrane is called the Singer-Nicholson fluid mosaic model
This model was first proposed in by Singer-Nicolson in 1972
Before then Davson-Danielli model was widely accepted …

36. Proteins Pore Phospholipids Davson-Danielli Model
1.3.S2 Analysis of evidence from electron microscopy that led to the proposal of the Davson-Danielli model.
The evidence: In high magnification electron micrographs membranes appeared as two dark parallel lines with a lighter coloured region in between.
Proteins appear dark in electron micrographs and phospholipids appear light - possibly indicating proteins layers either side of a phospholipid core.
Pore
Proteins
Phospholipids
Davson-Danielli
Model
The model:
A protein-lipid sandwich
Lipid bilayer composed of phospholipids (hydrophobic tails inside, hydrophilic heads outside)
Proteins coat outer surface
Proteins do not permeate the lipid bilayer
This explains: Despite being very thin membranes are an effective barrier to the movement of certain substances.

37. Falsification of the Davson-Danielli model
1.3.S3 Analysis of the falsification of the Davson-Danielli model that led to the Singer-Nicolson model.
Falsification of the Davson-Danielli model
– freeze fracturing
This technique involves rapid freezing of cells and then fracturing them.
Interpreting the image:
The fracture occurs along lines of weakness, including the centre of membranes.
The fracture reveals an irregular rough surface inside the phospholipid bilayer
The globular structures were interpreted as trans-membrane proteins.
Conclusion:
This is contrary to the Davson-Danielli model which only involves proteins coating the surface of the membrane. A new model is needed to explain the presence of as trans-membrane proteins.

38. Setting it Straight Hormone versus Steroid Cholesterol versus Steroid
A steroid hormone is a steroid that acts as a hormone. Steroid hormones can be grouped into two classes: corticosteroids (typically made in the adrenal cortex, hence cortico-) and sex steroids (typically made in the gonads or placenta).
Cholesterol versus Steroid
Steroids and their metabolites often function as signalling molecules (the most notable examples are steroid hormones), and steroids and phospholipids are components of cell membranes. Steroids such as cholesterol decrease membrane fluidity. Similar to lipids, steroids are highly concentrated energy stores

39. Setting it Straight Semipermeable versus selectively permeable
Semi-permeable membrane describes a membrane that allows some particles to pass through, where as the selectively permeable membrane "chooses" what passes through. Basically, selectively permeable membranes are very picky. Semipermeable membrane allows any substance/material to go through it.
Note – membranes are not just “cell” membranes BUT Cell membrane is selectively permeable that means that the cell membraneallows only selected molecules to pass through it for example gases ,small molecules etc.

40. Setting it Straight Fluidity vs Flexibility
Fluid means that the embedded proteins or carbohydrates attached to the cell membrane have the ability to move around within the membrane.
Flexible means its lipid bilayers would be able to bend easily
Fluidity does not mean flexible.
Cholesterol reduces fluidity (ability of proteins etc. to move within the membrane) and permeability, but increases the flexibility (lipids hold to gether more so can flex, but this means “things” can’t move through or within those layers as easily)

41. Bibliography / Acknowledgments
Jason de Nys