Plasma Membrane – Composition and Structure
What is known? Perspective
Surprisingly controversial – no one has
properly seen a membrane: microscopes
do not have high enough resolution
Cellular membranes are very-well
described through models, but our
molecular scale models are just models
– all molecular scale observations are
indirect
Many chemical and physical properties of cellular membranes, in accordance with
usual laws and theories of chemistry and physics, which in turn accurately
describe known features of microscopic and macroscopic biology
Living cell: a self-reproducing system of molecules held inside a container –
plasma membrane is simple in form: structure based on a double layer sheet of
lipid molecules ~5nm/50 atoms thick
The plasma membrane provides a large surface area for the cell – Area of the
plasma membrane (6.5% of total cell membrane) in 1 ml of tissue is about 0.56m 2
1ml of compact cells – a cube of membranes spread out to cover a square of
3x3m
What is the function/advantage of the plasma/biological membrane?
Important component of the cell!
Compartmentalisation: concentrations influence reaction rates and so specific
reactions can be encouraged or discouraged by setting boundaries
Evolution: defined and confined systems can be subjected to selection pressures
– together these properties are essential to the development and continuation
of terrestrial life as replicating nucleic acids and the stereo-specific, low
temperature catalysis achieved by enzymes
How do cellular membranes achieve this: properties derive from the components
of membranes – lipids, proteins, sugar, ions and water
Spontaneous formation of membranes
Lipid bilayer firmly established as the universal basis of membrane structure –
its properties are responsible for the general properties of all cell membranes
Cells are filled with and surrounded by solutions of molecules in water – Cell
membranes is a consequence of the way membrane lipids behave in an aqueous
environment
, Lipids in cell membranes combine 2 very different properties in a single
molecule: each lipid has a hydrophilic head and 1-2 hydrophobic hydrocarbon
tails
Most abundant lipids in cell membranes are phospholipids, molecules in which the
hydrophilic head is linked to the rest of the lipid through a phosphate group
Most common type of phospholipid in most cell membranes is phosphatidylcholine
Molecules with both hydrophilic and hydrophobic properties are amhipathic –
chemical property shared by other types of membrane lipids including sterols
(cholesterol etc.), glycolipids – crucial to driving these lipid molecules to
assemble into bilayers in an aqueous environment
Hydrophillic molecules dissolve readily in water as they contain charged atoms or
polar groups which can form electrostatic attractions or H-bonds with water
molecules
Hydrophobic molecules by contrast are insoluble in water because atoms are
mostly uncharged or non-polar cannot form favourable interactions with water
molecules – non-polar atoms force adjacent water molecules to reorganised into
a cagelike structure around the hydrophobic molecule - creation of a more
ordered structure than surrounding water requires energy
Energy cost is minimised, if hydrophobic molecules cluster together to limit
contact with water to the smallest possible number of water molecules: purely
hydrophobic molecules (eg. fats in animal fat cells and oils in plant seeds)
coalesce into a single large drop when dispersed in water
Amphipathic molecules subject to 2 conflicting forces: hydrophilic and
hydrophobic – 3 possible arrangements
achieved in the laboratory
a) Water/air interface
b) Micelle: if the cross-sectional area of
the tails is smaller than the head than
micelles are favoured
c) Bilayer: if the cross-sectional area of
the tails is equivalent to that of the head
then planar layers are favoured
- Arrangement that satisfies the forces and
energetically most favourable: hydrophilic
heads face the water from both surfaces
of the bilayer sheet; hydrophobic tails are
all shielded from the water as they lie next to one another in the interior
, - Phospholipids adjacent to another is solvating the other – planar shape
through crystallography – head group has high diffraction (high electron
density), fatty acid chains less
- Same forces that drive bilayer formation makes the bilayer self-healing – any
tear in the sheet will create a free edge that is exposed to water: because
this situation is energetically unfavourable the molecules of the bilayer will
spontaneously rearrange to eliminate the free edge
- If the tear is small – single continuous sheet restored, if tear is large – sheet
may begin to fold in on itself and break up into separate closed vesicles
- The prohibition on free edges has a profound consequence – only way a finite
sheet can avoid free edges is to bend and seal forming a boundary around a
closed space – essential for creation of a living cell, simply due to a property
of amphipaths
- Arguments for spontaneous formation of bilayers are largely thermodynamic –
many weak bonds and minimisation of entropy
Membrane Fluidity
Aqueous environment inside and outside
a cell prevents membrane lipids from
escaping the bilayer, nothing stops
these molecules moving within the plane
of the bilayer
Membrane behaves as a 2-dimensional fluid, crucial for membrane function and
integrity, membrane flexibility is different – ability to bend, sets lower limits of
~25nm to size of vesicle that cell membranes can form
Study of fluidity through synthetic lipid bilayers: produced by spontaneous
aggregation of amphipathic lipid molecules in water – liposomes/flat
phosopholipid bilayers can be formed across hole in partition between two
aqueous compartments
Allow measurements of the movements of the lipid molecules, revealing some
types of movement are rare while others are frequent and rapid – in synthetic
lipid bilayers phospholipid molecules rarely tumble from one half of the bilayer
or monolayer to the other
Without proteins to facilitate the process and conditions similar to those it a
cell, event of “flip-flop” occurs less than once a month for any individual lipid
molecule
Result of thermal motions: Lipid molecules however, exchange places with their
neighbours – exchange leads to rapid diffusion of lipid molecules in plane of the
membrane: if temperature is decreased, the drop in thermal energy decreases
the rate of lipid movement, making bilayer less fluid
, In reality, membranes are not
infinitely thin – they have 2 leaflets
- It is possible for lipids to also
diffuse between leaflets = flipping
- Takes a lot of energy, hence a rare
occurrence
- For lipids – flipping is slower than lateral diffusion – no reported cases for
flipping of proteins
- Flipping can be reversed by flipases
- Net result is the establishment of membrane asymmetry
Membranes can contain regions of local order (Quinn, 2009)
There are two sub-categories
- Bilayer formers : PC, SM, PS, PI, PG and few more
- Non-bilayer formers: PE and a few others – give water-filled tubes with polar
groups on the inside in hexagonal array called the hexagonal-II structure.
Protein-rich membranes are rich in non-bilayer forming lipids and the proteins and
other membrane constituents probably constrain these lipids into a bilayer
formation.
Functions of local membrane regions…
Non-bilayer lipids and high-melting point lipids give lateral phase separations as
temperature is reduced and fluidity decreases.
Particles – probably intrinsic membrane proteins – are pushed to the periphery of the
gel phase. Some particles are missing - have they been ejected into the aqueous phase
or “melted” into a non-particulate form?
Poikilotherms adapt to temperature by adjusting their membrane lipid composition in
order to avoid phase transitions.
If phase transitions occur on cooling, then re-warming allows the gel phase regions to
to adopt porous non-bilayer structures that compromise membranes transport
selectivity and kill the cells through “cold shock” (Synecoccus thermally quenched for
15oC and freeze fractured for EM)
Membrane Rafts
Some membrane structures and sub-domains can be preserved by extraction in cold
detergents or released by sonication.
What is known? Perspective
Surprisingly controversial – no one has
properly seen a membrane: microscopes
do not have high enough resolution
Cellular membranes are very-well
described through models, but our
molecular scale models are just models
– all molecular scale observations are
indirect
Many chemical and physical properties of cellular membranes, in accordance with
usual laws and theories of chemistry and physics, which in turn accurately
describe known features of microscopic and macroscopic biology
Living cell: a self-reproducing system of molecules held inside a container –
plasma membrane is simple in form: structure based on a double layer sheet of
lipid molecules ~5nm/50 atoms thick
The plasma membrane provides a large surface area for the cell – Area of the
plasma membrane (6.5% of total cell membrane) in 1 ml of tissue is about 0.56m 2
1ml of compact cells – a cube of membranes spread out to cover a square of
3x3m
What is the function/advantage of the plasma/biological membrane?
Important component of the cell!
Compartmentalisation: concentrations influence reaction rates and so specific
reactions can be encouraged or discouraged by setting boundaries
Evolution: defined and confined systems can be subjected to selection pressures
– together these properties are essential to the development and continuation
of terrestrial life as replicating nucleic acids and the stereo-specific, low
temperature catalysis achieved by enzymes
How do cellular membranes achieve this: properties derive from the components
of membranes – lipids, proteins, sugar, ions and water
Spontaneous formation of membranes
Lipid bilayer firmly established as the universal basis of membrane structure –
its properties are responsible for the general properties of all cell membranes
Cells are filled with and surrounded by solutions of molecules in water – Cell
membranes is a consequence of the way membrane lipids behave in an aqueous
environment
, Lipids in cell membranes combine 2 very different properties in a single
molecule: each lipid has a hydrophilic head and 1-2 hydrophobic hydrocarbon
tails
Most abundant lipids in cell membranes are phospholipids, molecules in which the
hydrophilic head is linked to the rest of the lipid through a phosphate group
Most common type of phospholipid in most cell membranes is phosphatidylcholine
Molecules with both hydrophilic and hydrophobic properties are amhipathic –
chemical property shared by other types of membrane lipids including sterols
(cholesterol etc.), glycolipids – crucial to driving these lipid molecules to
assemble into bilayers in an aqueous environment
Hydrophillic molecules dissolve readily in water as they contain charged atoms or
polar groups which can form electrostatic attractions or H-bonds with water
molecules
Hydrophobic molecules by contrast are insoluble in water because atoms are
mostly uncharged or non-polar cannot form favourable interactions with water
molecules – non-polar atoms force adjacent water molecules to reorganised into
a cagelike structure around the hydrophobic molecule - creation of a more
ordered structure than surrounding water requires energy
Energy cost is minimised, if hydrophobic molecules cluster together to limit
contact with water to the smallest possible number of water molecules: purely
hydrophobic molecules (eg. fats in animal fat cells and oils in plant seeds)
coalesce into a single large drop when dispersed in water
Amphipathic molecules subject to 2 conflicting forces: hydrophilic and
hydrophobic – 3 possible arrangements
achieved in the laboratory
a) Water/air interface
b) Micelle: if the cross-sectional area of
the tails is smaller than the head than
micelles are favoured
c) Bilayer: if the cross-sectional area of
the tails is equivalent to that of the head
then planar layers are favoured
- Arrangement that satisfies the forces and
energetically most favourable: hydrophilic
heads face the water from both surfaces
of the bilayer sheet; hydrophobic tails are
all shielded from the water as they lie next to one another in the interior
, - Phospholipids adjacent to another is solvating the other – planar shape
through crystallography – head group has high diffraction (high electron
density), fatty acid chains less
- Same forces that drive bilayer formation makes the bilayer self-healing – any
tear in the sheet will create a free edge that is exposed to water: because
this situation is energetically unfavourable the molecules of the bilayer will
spontaneously rearrange to eliminate the free edge
- If the tear is small – single continuous sheet restored, if tear is large – sheet
may begin to fold in on itself and break up into separate closed vesicles
- The prohibition on free edges has a profound consequence – only way a finite
sheet can avoid free edges is to bend and seal forming a boundary around a
closed space – essential for creation of a living cell, simply due to a property
of amphipaths
- Arguments for spontaneous formation of bilayers are largely thermodynamic –
many weak bonds and minimisation of entropy
Membrane Fluidity
Aqueous environment inside and outside
a cell prevents membrane lipids from
escaping the bilayer, nothing stops
these molecules moving within the plane
of the bilayer
Membrane behaves as a 2-dimensional fluid, crucial for membrane function and
integrity, membrane flexibility is different – ability to bend, sets lower limits of
~25nm to size of vesicle that cell membranes can form
Study of fluidity through synthetic lipid bilayers: produced by spontaneous
aggregation of amphipathic lipid molecules in water – liposomes/flat
phosopholipid bilayers can be formed across hole in partition between two
aqueous compartments
Allow measurements of the movements of the lipid molecules, revealing some
types of movement are rare while others are frequent and rapid – in synthetic
lipid bilayers phospholipid molecules rarely tumble from one half of the bilayer
or monolayer to the other
Without proteins to facilitate the process and conditions similar to those it a
cell, event of “flip-flop” occurs less than once a month for any individual lipid
molecule
Result of thermal motions: Lipid molecules however, exchange places with their
neighbours – exchange leads to rapid diffusion of lipid molecules in plane of the
membrane: if temperature is decreased, the drop in thermal energy decreases
the rate of lipid movement, making bilayer less fluid
, In reality, membranes are not
infinitely thin – they have 2 leaflets
- It is possible for lipids to also
diffuse between leaflets = flipping
- Takes a lot of energy, hence a rare
occurrence
- For lipids – flipping is slower than lateral diffusion – no reported cases for
flipping of proteins
- Flipping can be reversed by flipases
- Net result is the establishment of membrane asymmetry
Membranes can contain regions of local order (Quinn, 2009)
There are two sub-categories
- Bilayer formers : PC, SM, PS, PI, PG and few more
- Non-bilayer formers: PE and a few others – give water-filled tubes with polar
groups on the inside in hexagonal array called the hexagonal-II structure.
Protein-rich membranes are rich in non-bilayer forming lipids and the proteins and
other membrane constituents probably constrain these lipids into a bilayer
formation.
Functions of local membrane regions…
Non-bilayer lipids and high-melting point lipids give lateral phase separations as
temperature is reduced and fluidity decreases.
Particles – probably intrinsic membrane proteins – are pushed to the periphery of the
gel phase. Some particles are missing - have they been ejected into the aqueous phase
or “melted” into a non-particulate form?
Poikilotherms adapt to temperature by adjusting their membrane lipid composition in
order to avoid phase transitions.
If phase transitions occur on cooling, then re-warming allows the gel phase regions to
to adopt porous non-bilayer structures that compromise membranes transport
selectivity and kill the cells through “cold shock” (Synecoccus thermally quenched for
15oC and freeze fractured for EM)
Membrane Rafts
Some membrane structures and sub-domains can be preserved by extraction in cold
detergents or released by sonication.
