1.

3 Membrane structure
Essential idea: The structure of biological membranes makes them fluid and dynamic.
Nature of Science: Using models as representations of the real world—there are
alternative models of membrane structure. (1.11) Falsification of theories with one
theory being superseded by another—evidence falsified the Davson-Danielli model.
(1.9)
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.

By Chris Paine
https://bioknowledgy.weebly.com/
Understandings, Applications and Skills
Statement Guidance
1.3.U1 Phospholipids form bilayers in water due to the Amphipathic phospholipids have hydrophilic
amphipathic properties of phospholipid molecules. 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.
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?
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
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) It’s
composed of a glycerol
and a phosphate molecule.

• The tails are hydrophobic

(repelled by water). They
are composed of fatty acid
(hydrocarbon) chains.

• Because phospholipids
contain both hydrophilic
(water-loving) and lipophilic
(fat-loving) regions, they are
classed as amphipathic
When drawing a diagram of a
phospholipid this is a good
example which shows all the
key features.
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
1.3.U1 Phospholipids form bilayers in water due to the amphipathic properties of phospholipid molecules.

Phospholipid Structure
• Phospholipids may vary in the length and relative
saturation of the fatty acid tails.
• Shorter fatty acid tails will increase fluidity as they are less
viscous and more susceptible to changes in kinetic energy.
• Lipid chains with double bonds (unsaturated fatty acids)
have kinked hydrocarbon tails that are harder to pack
together.
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.
1.3.U1 Phospholipids form bilayers in water due to the amphipathic properties of phospholipid molecules.

Arrangement of phospholipids
in Membranes:

1. Phospholipids
spontaneously arrange
into a bilayer.
2. The hydrophobic tail
regions face inwards and
are shielded from the
surrounding polar fluids,
while the two hydrophilic
head regions associate
with the cytoplasm and
extracellular fluids
respectively.
1.3.U1 Phospholipids form bilayers in water due to the amphipathic properties of phospholipid molecules.

Properties of the Phospholipid Bilayer:

1. The bilayer is held together by

weak hydrophobic interactions
between the tails
2. Hydrophilic / hydrophobic layers
restrict the passage of many
substances.
3. Individual phospholipids can move
within the bilayer, allowing for
membrane fluidity and flexibility
4. This fluidity allows for the
spontaneous breaking and
reforming of membranes
(endocytosis / exocytosis)

Note: 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.

But wait! there’s more!

The plasma membrane is not just made of
phospholipids
1.3.U2 Membrane proteins are diverse in terms of structure, position in the membrane and function.

Proteins:
1. Integral proteins are permanently embedded, many go all the way through
and are polytopic (poly = many, topic = surface), integral proteins penetrating
just one surface are monotopic.

2. Peripheral proteins usually have a temporary association with the membrane

by non-covalent interactions, they can be monotopic or attach to the surface
of the membrane.  
1.3.U2 Membrane proteins are diverse in terms of structure, position in the membrane and function.

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

1. Transport: Protein channels (facilitated) and protein pumps (active –require energy)

2. Receptors: Peptide-based hormones (insulin, glucagon, etc.)

3. Anchorage: Cytoskeleton attachments and extracellular matrix

4. Cell recognition: glycoproteins- MHC (immune) proteins and antigens

5. Intercellular joinings: Tight junctions and plasmodesmata

6. Enzymatic activity: Metabolic pathways (e.g. electron transport chain)

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

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

o The remainder of the molecule (steroid

ring and hydrocarbon tail) is hydrophobic
and associates with the phospholipid tails.
1.3.U3 Cholesterol is a component of animal cell membranes.

Cholesterol
Hydroxyl group (OH) makes the
head polar and hydrophilic -
attracted to the phosphate heads
on the periphery of the membrane.

Carbon rings –
cholesterol is a steroid.

Non-polar (hydrophobic) tail –attracted

to the hydrophobic tails of phospholipids
in the centre of the membrane
1.3.U3 Cholesterol is a component of animal cell membranes.

Cholesterol
• Cholesterol acts as a bi-directional regulator of
membrane fluidity.
• At high temperatures it stabilises the membrane and raises the
melting point 
• At low temperatures it intercalates between the phospholipids
and prevents clustering
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
1.3.A1 Cholesterol in mammalian membranes reduces membrane fluidity and permeability to some solutes.

Cholesterol’s role in
membrane fluidity
1. The presence of
cholesterol in the
membrane restricts the
movement of
phospholipids and other
molecules – this reduces
membrane fluidity.

2. The presence of cholesterol

disrupts the regular packing 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
3. hydrophilic/water soluble molecules and
ions such as sodium and hydrogen that would
otherwise freely cross.
Cholesterol helps secure peripheral proteins
4. by forming high density lipid rafts capable of
anchoring the protein.
1.3.S1 Drawing of the fluid mosaic model.

Use the tutorials to learn and

review membrane structure

http://www.bio.davidson.edu/people/macampbell/111/
memb-swf/membranes.swf

http://www.phschool.com/science/biology_place/biocoach/biomembrane1/
regions.html

https://www.wisc-online.com//LearningContent/ap1101/index.html
 Reminder of features that make good
diagrams:
• Good use of space • Lines touch the labeled
• Clear strong lines structure
• Label lines are straight • No unnecessary shading or
• Labels clearly written colouring
• (Scale bar if appropriate)
1.3.S1 Drawing of the fluid mosaic model.

Reminder of features that make good diagrams:

• 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
http://www.youtube.com/watch?v=w9VBHGNoFrY
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.

Proteins Pore
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
Phospholipids
(permeate means “to spread through
something”)
Describe the observations and conclusions drawn by Davson and
Danielli in discovering the structure of cell membranes.

The Davson-Danielli
model of the cell
membrane is
described as a
protein-lipid-protein
"sandwich." This
structure was
proposed because Although structurally incorrect,
through an electron the Davson-Danielli model
microscope the cell Proteins show up
increased understanding of cell
membranes by including
membrane appears dark under the
electron microscope- proteins in biological
as two dark lines with lipids showing
membranes.
up clear.
(proposed to be the
proteins) on either
side of a lighter core
(proposed to be the
lipid bilayer)
Today we know that the membrane is highly permeable to non-polar (fat-
soluble) molecules. Davson-Danielli model did not take this into account.
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

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-
This technique involves rapid freezing of cells membrane proteins.
and then fracturing them.

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.
Describe conclusions about cell membrane structure drawn from freeze-etched
electron micrograph images of the cell membrane.

Freeze etching is an electron microscopic preparation

technique that was developed in the 1960's. The technique
involves rapid freezing of cells and then fracturing them along
lines of weakness, including through the center of membranes.
Describe conclusions about cell membrane structure drawn from freeze-etched
electron micrograph images of the cell membrane.

Globular structures scattered through freeze-etched images of

the center of membranes were interpreted as integral
(transmembrane) proteins.
Describe conclusions about cell membrane structure drawn from freeze-etched
electron micrograph images of the cell membrane.

Davson-Danielli Model New Evidence

The cell membrane proteins are all The cell membrane proteins can span
peripheral to the lipid bilayer. through the lipid bilayer.
Describe conclusions about cell membrane structure drawn from improvements
in techniques for determining the structure of membrane proteins.

Improvements in biochemical
techniques allowed proteins to be
extracted from membranes. The
proteins were found to be:
• varied in size, unlike the type of
protein that would form
continuous layers on the outside
of the membrane as Davson and
Danielli had proposed.
• hydrophobic on at least part of
their surface, unlike the
completely hydrophilic proteins on
the outside of the membrane as
Davson and Danielli had
proposed.
Describe conclusions about cell membrane structure
drawn from cell fusion experiments.

Frye and Edidin (1970) fused two cells labeled with

different membrane-bound fluorescent tags and
watched as the two protein populations mixed.
Describe conclusions about cell membrane structure drawn from cell fusion
experiments.
Red or green fluorescent markers
were attached to mouse and human
membrane proteins (essentially Within 40 minutes
“staining” the proteins in the the proteins were
Mouse and membrane so they could be tracked mixed throughout
human and identified). the membrane of
cells were the fused cell.
fused
together.
Describe conclusions about cell membrane structure drawn from cell fusion
experiments.

Davson-Danielli Model New Evidence

The cell membrane proteins form a Membrane proteins can move around
rigid, non-moving layer on either side within the bilayer, they are not locked
of the lipid bilayer. in place.
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 All of this was supported by observations from
the now more powerful electron microscope.
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 insoluble (indicating
hydrophobic surfaces). These
proteins were also very varied
in size and globular in shape.

• Such proteins would be unable

to form continuous layers on
the periphery of the membrane
(they were irregular).

• The membrane proteins had hydrophobic regions and therefore

would embed in the membrane not layer the outside.
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
• Membrane proteins from
two different cells were
tagged with red and green
fluorescent markers
respectively.
• Red or green fluorescent
markers attached to
antibodies which would bind
• Within 40 minutes the red and green markers were
to membrane proteins.
mixed throughout the membrane of the fused cell.
• The membrane proteins of some • This showed that membrane proteins are free to
cells were tagged with red move within the membrane rather than being fixed
markers and other cells with in a peripheral layer as per Davson-Danielli.
green markers.
• The cells were fused together.
Compare the Davson-Danielli model of membrane
structure with the Singer-Nicolson model

As evidence mounted which

undermined the Davson-Danielli model
of membrane structure, S. Jonathan
Singer and Garth Nicolson (1972)
proposed the fluid mosaic model of the
cell membrane. The Singer-Nicolson
model has two key features—a mosaic
of proteins embedded in the membrane,
and the membrane being a fluid bilayer
of lipids. The lipid bilayer suggestion
agrees with previous models but the
Singer-Nicolson model includes
proteins as globular structures that can
embedded in the layer rather than
forming sheets on the membrane
1.3.S3 Analysis of the falsification of the Davson-Danielli model that led to the Singer-Nicolson model.

Davson-Danielli Model Singer-Nicolson Model

◎ The “Lipid Sandwich ◎ The “Fluid Mosaic Model.”
Model.” ◎ Membranes are fluid,
◎ Membranes are static, meaning they can change
rigid and fixed. shape and flow
◎ Lipids are capped with a ◎ Proteins are dispersed
layer of proteins. throughout the membrane,
◎ All proteins are leaving many portions of the
hydrophilic and peripheral lipid bare and exposed to the
to the lipid bilayer. extra- and intracellular
environments.
◎ Proteins are peripheral and
integral to the lipid bilayer.
*scientific models change as new information is Integral proteins have
gleaned from technological and experimental
advancements (1.3.NOS1)
hydrophobic regions.
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….

Understandings, Applications and Skills
Statement Guidance
1.3.U1 Phospholipids form bilayers in water due to the Amphipathic phospholipids have hydrophilic
amphipathic properties of phospholipid molecules. 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.