The structure of biological membranes allows them to be fluid and dynamic. Membranes are made of a phospholipid bilayer with proteins and cholesterol embedded within. Phospholipids form bilayers due to their amphipathic properties - their hydrophobic tails orient inward while hydrophilic heads remain on the outer surfaces. Membrane proteins perform diverse functions and can be integral or peripheral. Cholesterol increases membrane stability while reducing fluidity. Early models of membrane structure proposed protein layers sandwiching the bilayer, but evidence demonstrated proteins are mobile within the bilayer, leading to the current fluid mosaic model.

1. By Chris Paine
https://bioknowledgy.weebly.com/
1.3 Membrane Structure
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 https://bioknowledgy.weebly.com/
and Bioninja.com
http://www.europhysicsnews.org/doc_journal/images/epn/hl/435/Sommer.jpg
Edited By Eran Earland

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. http://www.flickr.com/photos/zorin-denu/5385963280/
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.

4. http://www.flickr.com/photos/zorin-denu/5385963280/
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
1.3.U1 Phospholipids form bilayers in water due to the amphipathic properties of phospholipid
molecules.

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. 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)
1.3.U1 Phospholipids form bilayers in water due to the amphipathic properties of phospholipid
molecules.
http://upload.wikimedia.org/wikipedia/commons/3/39/Phospholipid_TvanBrussel.jpg
http://www.ib.bioninja.com.au/_Media/phospholipid_bilayer_med.jpeg
When drawing a diagram of a
phospholipid this is a good example
which shows all the key features

7. When put into water, an emergent property is that
phospholipids will self-organise to keep their heads ‘wet’
and their tails ‘dry’
micelle liposome
1.3.U1 Phospholipids form bilayers in water due to the amphipathic properties of phospholipid
molecules.
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. http://commons.wikimedia.org/wiki/File:Phospholipids_aqueous_solution_structures.svg
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
1.3.U1 Phospholipids form bilayers in water due to the amphipathic properties of phospholipid
molecules.

9. 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)
1.3.U1 Phospholipids form bilayers in water due to the amphipathic properties of phospholipid
molecules.

10. But wait! there’s more!
The plasma membrane is not just made of
phospholipids
http://commons.wikimedia.org/wiki/File:Cell_membrane_detailed_diagram_en.svg?uselang=en-gb
1.3.U1 Phospholipids form bilayers in water due to the amphipathic properties of phospholipid
molecules.

11. Proteins:
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
1.3.U2 Membrane proteins are diverse in terms of structure, position in the membrane
and function.
http://commons.wikimedia.org/wiki/File:Cell_membrane_detailed_diagram_en.svg?uselang=en-gb

12. Connections to Topic 2.4 – Proteins
http://ib.bioninja.com.au/standard-level/topic-2-molecular-biology/24-proteins/
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.au/standard-level/topic-2-molecular-biology/24-proteins/
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
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
1.3.U2 Membrane proteins are diverse in terms of structure, position in the membrane
and function.

15. Cell Membrane Protein Functions

16. 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
http://commons.wikimedia.org/wiki/File:Cell_membrane_detailed_diagram_en.svg?uselang=en-gb
1.3.U2 Membrane proteins are diverse in terms of structure, position in the membrane
and function.

17. 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)
http://www.ib.bioninja.com.au/standard-level/topic-2-cells/24-membranes.html

18. 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…
1.3.U3 Cholesterol is a component of animal cell membranes.

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. Cholesterol
1.3.U3 Cholesterol is a component of animal cell membranes.
http://www.cholesterol-and-health.com/images/Cholesterol_Structure.jpg
http://www.uic.edu/classes/bios/bios100/lectf03am/cholesterol.jpg
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. Membrane fluidity
1.3.A1 Cholesterol in mammalian membranes reduces membrane fluidity and
permeability to some solutes.
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
http://www.nature.com/scitable/content/ne0000/ne0000/ne0000/ne0000/14668965/U2.cp5.3_membrane_f2.jpg
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.

22. Cholesterol’s role in
membrane fluidity
1.3.A1 Cholesterol in mammalian membranes reduces membrane fluidity and
permeability to some solutes.
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.
Cholesterol also reduces the permeability
to hydrophilic/water soluble molecules
and ions such as sodium and hydrogen.
2.
3.
http://www.nature.com/scitable/content/ne0000/ne0000/ne0000/ne0000/14668965/U2.cp5.3_membrane_f2.jpg
The presence of
cholesterol in the
membrane restricts the
movement of
phospholipids and other
molecules – this reduces
membrane fluidity.
1.

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.
https://www.wisc-online.com//LearningContent/ap1101/index.html
http://www.phschool.com/science/biology_place/biocoach/biomembrane1/regi
ons.html
http://www.bio.davidson.edu/people/macampbell/111/memb-
swf/membranes.swf
Use the tutorials to learn and
review membrane structure

25. 1.3.S1 Drawing of the fluid mosaic model.
http://www.youtube.com/watch?v=w9VBHGNoFrY

26. 1.3.S1 Drawing of the fluid mosaic model.
http://www.ib.bioninja.com.au/_Media/phospholipid_bilayer_med.jpeg
• 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. • 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)
1.3.S2 Analysis of evidence from electron microscopy that led to the proposal of the
Davson-Danielli model.

28. • 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
1.3.S2 Analysis of evidence from electron microscopy that led to the proposal of the
Davson-Danielli model.

29. 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
1.3.S3 Analysis of the falsification of the Davson-Danielli model that led to the Singer-
Nicolson model.

30. 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
1.3.S3 Analysis of the falsification of the Davson-Danielli model that led to the Singer-
Nicolson model.

31. 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)
1.3.S3 Analysis of the falsification of the Davson-Danielli model that led to the Singer-
Nicolson model.

32. Our current model of the cell membrane is called the Singer-Nicholson
fluid mosaic model
http://commons.wikimedia.org/wiki/File:Cell_membrane_detailed_diagram_en.svg?uselang=en-gb
1.3.S3 Analysis of the falsification of the Davson-Danielli model that led to the Singer-
Nicolson 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. Our current model of the cell membrane is called the Singer-Nicholson
fluid mosaic model
There is strong evidence for this model:
http://commons.wikimedia.org/wiki/File:Cell_membrane_detailed_diagram_en.svg?uselang=en-gb
1.3.S3 Analysis of the falsification of the Davson-Danielli model that led to the Singer-
Nicolson 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. Our current model of the cell membrane is called the Singer-Nicholson
fluid mosaic model
There is strong evidence for this model:
http://commons.wikimedia.org/wiki/File:Cell_membrane_detailed_diagram_en.svg?uselang=en-gb
1.3.S3 Analysis of the falsification of the Davson-Danielli model that led to the Singer-
Nicolson model.
Fluorescent antibody
tagging
• 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.
• 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.
• The cells were fused together.

35. Our current model of the cell membrane is called the Singer-Nicholson
fluid mosaic model
http://commons.wikimedia.org/wiki/File:Cell_membrane_detailed_diagram_en.svg?uselang=en-gb
1.3.S3 Analysis of the falsification of the Davson-Danielli model that led to the Singer-
Nicolson model.
This model was first proposed in by Singer-Nicolson in 1972
Before then Davson-Danielli model was widely accepted …

36. 1.3.S2 Analysis of evidence from electron microscopy that led to the proposal of the
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
http://www.cytochemistry.net/cell-biology/EMview.jpg
PoreProteins
Phospholipids
This explains: Despite being very thin membranes are an
effective barrier to the movement of certain substances.
http://upload.wikimedia.org/wikipedia/commons/6/69/Davson_danielli_miguelferig.jpg
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.
Davson-Danielli
Model

37. 1.3.S3 Analysis of the falsification of the Davson-Danielli model that led to the Singer-
Nicolson model.
http://www.cytochemistry.net/cell-biology/ffimage.jpg
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.
Falsification of the Davson-Danielli model
– freeze fracturing
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
– 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