Site author Richard Steane
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Transport across cell membranes

Structure of cell membranes

Cell surface membranes (plasma membranes) share the same basic structure as that of internal membranes surrounding organelles. This is the situation in all eukaryotic organisms - animals, plants and fungi - although plants and fungi usually also have a cell wall on the outside of the cell membrane. Prokaryotes have slightly different surface membranes and cell walls, and no internal organelles.

Membranes are composed of a number of molecules, each with a distinct three-dimensional structure:

An electron micrograph of the plasma membrane (of Chara corallina (cropped from [1]). To fix the membrane for electronmicroscopy the material was crosslinked using OsO 4
An electron micrograph of the plasma membrane of Chara corallina

The cell membrane is too thin to show any detail when seen with a light microscope. Its thickness is about 5-10 nm.
The electron microscope does not usually show much detail. Often there is just a pair of dark lines with a lighter inner area.


The main components of cell membranes are phospholipids. These molecules have a hydrophilic head section and a hydrophobic tail section.

Collectively they form a double layer - a phospholipid bilayer - with the phosphate heads projecting out on either side of the membrane, into the two aqueous environments of the extracellular fluid and the cytoplasm (cytosol). Sandwiched between these are the fatty acid tails, stacked alongside one another and in contact with the tips of the other set of tails facing the opposite direction.

bilayer (2K)

Embedded in (both halves of) the bilayer are likely to be molecules of cholesterol. The main section (four rings) of the cholesterol molecule is hydrophobic, and the -OH group projecting from one end of it is hydrophilic. This causes the cholesterol molecule to become aligned with the phospholipids on each side of the bilayer. The proportion of cholesterol to phospholipids varies in different cells, and this changes the physical state of the membrane - reducing its fluidity by restricting the sideways movement of phospholipids and other molecules.

How thin can you spread your lipids?

Red blood cells

rbcsample (296K)

Red blood cells are ideal candidates for this sort of study
Now you have seen a few ghosts ! ghosts (36K)

These are the empty outer membranes of red blood cells.
In 1924 Gorter and Grendel extracted lipid from the cell membranes of red blood cells of several mammalian species. By spreading this on another liquid, they established the area occupied by a single molecular layer - a monolayer. When they divided this area by the observed external area of the cells, they consistently found a factor of 2, leading to the conclusion that lipids were arranged in a bilayer in cell membranes.

Can you think why red blood cells are so suitable for this? > nucleus

> Easily available (using a needle and syringe)
> Can be concentrated into a pellet by centrifuging
> Can be burst by exposure to hypotonic solution or water
> No nucleus, mitochondria, endoplasmic reticulum


A number of different proteins may be embedded in the phospholipid bilayer, interacting with the hydrophilic outer layers or the hydrophobic inner section. Some span both layers of the membrane and some only one, whilst others attach themselves to one or the other outer surface.

There are a number of membrane-spanning proteins that are involved in the transport of different substances across membranes.
Channels have two states: they can be either open or closed, and this change in shape is described as a conformational change.
Carrier proteins bind briefly with the substance they transport.
Channel proteins and carrier proteins are responsible for the specificity of the different transport mechanisms involved.
Pores are open to both sides of the membrane. Some pores are produced by chemical toxins.

Proteins within the membrane are described as intrinsic; those on the outside are called extrinsic.

Many transmembrane proteins are known. These typically have a barrel-like shape, composed of several alpha-helical sections ('domains') which locate themselves within the phospholipid bilayer, and they have hydrophobic side-chains. Between these section are short sections of peptides which interact with the aqueous environments of the extracellular fluid and cytosol. Other sections - often composed of charged amino acid residues - act as receptors or selectivity filters within the central channel.

Other protein channels are composed of sections of beta-pleated sheet.

Glycoproteins and glycolipids

These compounds consist of short, possibly branched, chains of carbohydrates (oligosaccharides) projecting out from proteins or lipids which are anchored in the surface of the bilayer.

They may act as antigens and be involved in identification of different cell types in the body, and possibly they may be implicated in the entry of pathogens into cells.

Cell_membrane_diagram3colour (121K)
Structural elements within the cell surface membrane

ABO blood group antigens are displayed on the surface of red blood cells (erythrocytes), as well as T cells, B cells, and platelets. They consist of a few sugar residues, some not often seen, and linked in different ways.

hantigen (1K) aantigen (2K) bantigen (2K)
key (1K)
The R group to which each of these oligosaccharide chains may be attached could be either protein (making glycoprotein), lipid (glycolipid) or even sphingolipid (glycosphingolipid).
Images courtesy University of Wisconsin

In contrast, Rhesus antigens are superficial proteins.

The fluid mosaic model

The various component molecules within cell membranes appear to fit together at the surface like the tesserae that make up the pattern or image of a mosaic.

However it is not a fixed structure and the components can can move in a number of ways, from side to side so they can spread out, or they can rotate. This gives the membrane the physical flexibility which is essential for its biological role of enveloping the cell and cell contents. In addition, the makeup of the membrane may change quite rapidly as other components are added to or taken away in response to the cell's functioning.

It is worth mentioning that within the inner membranes of both mitochondria and chloroplasts, electrons are picked up by certain carrier compounds, mostly quinones, and moved sideways within the membrane to the various enzyme complexes and photosystems of these organelles. These act as carrier proteins transferring protons (hydrogen ions) across the membranes. The electron carriers are effectively in solution within the hydrophobic inner lipid sections.

mosaic-04 (65K) A nice mosaic with a Biological feel, but it is rather static

Movement across membranes

Simple diffusion

Do not say movement 'across' or 'along' a concentration gradient
Diffusion is a passive process relying on migration of particles in three dimensions. It does not require energy. Certain molecules can diffuse fairly easily across membranes, from a region of higher to a region of lower concentration, i.e. moving down a concentration gradient.

simple_diffusion (41K)

To do this, they must associate themselves with the outer layer - not much of a barrier - and pass though the inner lipid section, and this transfer will be affected by their relative solubility in water versus solubility in oil/lipid.

Small polar uncharged molecules like water H2O and ethanol C2H5OH can pass through (fairly slowly), but larger polar molecules like glucose C6H12O6 and smaller charged molecules cannot pass at all. This includes ions like Na+, Cl- and K+ . Gases, e.g oxygen O2 and carbon dioxide CO2, can also diffuse through easily.

Diffusion of gases across a cell membrane

In fact this could be across the outer membrane of a mitochondrion (inside a cell)

O2CO2 (26K)
Why do oxygen (O2) and carbon dioxide (CO2) move in opposite directions?
> Oxygen moves from high concentration outside cell to lower concentration inside,
Carbon dioxide moves from high concentration inside cell to lower concentration inside,

Substances with a higher partition coefficient (relative affinity of a substance for lipid versus water) will pass more quickly through phospholipid membranes.

The viscosity of the inner lipid section is much greater than that of water, so it slows down the movement. It may be seen as a rate-limiting step in the transfer process.

Facilitated diffusion

This form of diffusion also relies on differences in concentration, but it is assisted by channel proteins or carrier proteins which are specific to the substance crossing the membrane.

There is a narrow gap in the middle of a channel protein through which only the target substance can pass, possibly after interaction with amino-acid sidechains which provide the specificity. For small substances, the rate of this diffusion can be quite high.

facilitatedchannel (43K)

Larger polar molecules like glucose can pass through specific carrier proteins which change shape as their target molecule passes through, again moving down its concentration gradient. This is not such a fast process.

Facilitated diffusion of glucose across a cell membrane

triangle (1K) facilitatedglucose (56K)

Channel proteins may be gated, i.e. open or close in response to prevailing conditions.
Voltage-gated ion channels allow specific ions e.g. Na+, K+, Ca2+, or Cl- to cross the membrane down their concentration gradient in response to changes in membrane potential.
Ligand-gated channels open when a chemical substance, e.g. a neurotransmitter, binds to part of them - usually called a receptor.

Both of these channel types are involved in the passage of nerve impulses along and between neurones.

Glucose transporters

GLUTs are carrier proteins embedded in cell membranes that can allow glucose (or fructose or galactose) to pass from one side to the other, depending on the relative concentrations. There are 14 different types known, each with slightly different properties. These do not require ATP, as the facilitated diffusion relies on a concentration gradient. Other glucose transport proteins (co-transporters, such as the glucose symporters SGLT1 and SGLT2) use a concentration gradient of sodium ions which is established by active transport. See the section below.

Polypeptide chains of GLUTs consist of 12 helical sections alternating in direction within the phospholipid bilayer, with both the N-terminal and C-terminal ends pointing into the cytoplasm. There is a glucose binding site which changes conformation ( the 'alternate conformation' model) when glucose binds, so that glucose is released onto the opposite side of the membrane.

GLUT2 is involved in the intake of glucose into β cells within the pancreas, which respond by secreting the hormone insulin.

It is also present in the basolateral membrane of cells of the epithelium within the small intestine, so it is involved in the absorption of carbohydrate digestion products.

It is important in the control of blood glucose concentration. In liver cells glucose is taken up for glycogenesis (making glycogen) and released following glycogenolysis (breakdown of glycogen). These enzyme-controlled reactions are under the control of the hormones insulin and glucagon respectively.

Similarly, GLUT4 is expressed in striated muscle (skeletal muscle and cardiac muscle) and adipose (fat) tissues which take up glucose in response to insulin.


Osmosis is

Notes about concentration of water

At this level, it is best to refer to water potential, not water concentration or 'strength' of solutions
Water potential - ψ - is the 'measure of the ability of water molecules to move freely in a liquid', or the potential energy of water in a system compared to pure water.
Making a solution, by addition of solutes, reduces water potential.

Pure water has a water potential of 0 kPa, whilst solutions have negative water potential.
A 'weak solution' could have a water potential of -10 kPa and a more 'strong' solution could have a water potential of -100 kPa.
Put another way, water moves from a region with a certain water potential (higher water concentration) to one with a lower ( more negative) water potential (i.e. a lower water concentration).

The movement of water across membranes is somewhat paradoxical. We describe the lipid section of the phospholipid as hydrophobic - water hating - yet we say water can diffuse through it, and this is explained on the basis of a 'partition-diffusion model'. The efficiency of the transfer of water across membranes is probably a function of the high concentrations of water on either side of the bilayer. There are proteins which serve as channels allowing the entry of other substances into cells.

It was suspected that there must be specific pores in cell membranes that allow the passage of water. Some tissues show a greater permeability to water than others, and in some cases cells showed the ability to increase their permeability. This evidence suggested the existence of a specific water channel.


aquaporin (46K) In 1992 Peter Agre showed the molecular structure of a water channel called aquaporin in red blood cells and kidney tubules and he received the Nobel prize for this in 2003 . Other versions have been discovered in other cells, including plants.

It has been shown that a stream of water molecules passes very efficiently through these molecules.

Optimising osmosis in the kidney

ADH - antidiuretic hormone - also known as (arginine) vasopressin - AVP - is a hormone produced in neurones in the hypothalamus (on the undersurface of the brain) and it is passed down axons to the posterior pituitary and stored there in vesicles. If the tonicity of the surrounding extracellular fluid rises (water potential falls) - as a result of water being lost - ADH is released into the blood circulation and it passes to the kidneys.

ADH molecules bind to receptor proteins on cells lining the distal convoluted tubules and collecting ducts of nephrons in a kidney, and this causes aquaporins to be inserted into the membrane of these cells. The tertiary structure of this (aquaporin) protein gives a specific shape and size to the inside of the channel allowing (only) water to pass through. This effectively makes cell surface membranes much more permeable to water and so increases the reabsorption of water.

Water from the 'filtrate' inside the tubule enters the lining cells through the aquaporins by osmosis (diffusing down a water potential gradient) and it then passes from the lining cells into the surrounding capillaries via interstitial fluid, and consequently blood which is more diluted flows out via the renal vein and into the general circulation. This brings the water potential of blood back up to normal levels.

Presumably when the blood returns to normal tonicity, the level of ADH falls and aquaporins are removed from the membrane and returned to storage vesicles.

Active transport

Active transport requires the input of energy and a specialised carrier protein in order to 'pump' substances across membranes, against a concentration gradient.

Primary active transport involves ATP. This is hydrolysed by a carrier protein - so it may be called ATPase, as it acts as an enzyme.

In the process ATP → ADP + Pi, energy is released, which powers the movement. ATP provides a phosphate group which attaches to a specific site on the carrier protein, causing it to change in shape. This allows ions on one side of the membrane to enter and be deposited on the other side as the shape of the carrier changes back when the phosphate is removed.

A well-known example of this is the sodium-potassium ion pump (Na+/K+ ATPase) which is found in the membranes of all animal cells, where it is probably involved in controlling cell volume.

NaKpumpSummary (53K)

It is especially active in nerve cells (neurones) which require the establishment of an electrochemical membrane potential which is effectively reversed when a nervous impulse passes.

ATP is produced in aerobic respiration so active transport is dependent on the cell's metabolic activity and mitochondria. Respiratory inhibitors therefore have the effect of preventing active transport processes.

Sodium ions are exported from the nerve cell by active transport, and potassium ions are imported
The ratio is 3Na+:2K+

triangle (1K) NaKpumping (129K)
Click starts animation -
mouseover returns to start

The sodium-potassium ion pump protein changes conformation as a site is phosphorylated by ATP. For this reason it is also known as Na+/K+ ATPase


This is also called secondary active transport or indirect active transport.

It does not directly use ATP as an energy source, but rather it causes the movement of one substance together with another which has already established an electrochemical potential gradient after being transported using ATP as above. It also requires a specific carrier protein (cotransporter) which can accommodate both substances, and this movement is facilitated diffusion.

Thus, by one substance passing back across the membrane down its concentration gradient, it allows the passage of another substance across the membrane. In some cases, both substances pass across the membrane in the same direction; in others they move in opposite directions.

Co-transport of sodium ions and glucose
- both going in the same direction

symporterSGLT (1K)

In the absorption of sodium ions and glucose by epithelial cells lining the villi within the mammalian ileum ( section of inner membrane shown above), these cells have sodium ions actively pumped out of them on the outer surface membrane, so that the concentration of Na+ ions inside the cell is lower than in the lumen of the gut (the space containing food digestion products).
In other words, it maintains a diffusion gradient for Na+ ions from the lumen into the gut lining cells, and this provides a driving force for the entry of both sodium ions and glucose from the digested food via the symporter protein. (More details opposite)

Co-transport of sodium ions and calcium ions
- each going in opposite directions

antiportNaCa (40K)

This co-transport relies on the higher concentration of sodium ions outside the cell (above the membrane), thus an influx of sodium ions powers the exit of the calcium ions.

Secondary active transport may also be referred to as ion-coupled transport, and it often relies on sodium ions Na+ or protons H+ which are accumulated by ATP-driven active transport pumps..

There are two classes of secondary transfer, named according to the carrier protein and the direction of transport of the two substances involved. In each case, one substance powers the exchange by moving down its potential energy gradient, previously established by an ATP-powered pump.


Both substances are transported across the membrane in the same direction.

Co-transport mechanism for the absorption of glucose into the blood by a cell lining the ileum
jun16p2cotransport_corrected (46K) Suggest a name for the structures labelled with letters:
A: co-transport protein/glucose symporter/SGLT1
B: Na+/K+ ATPase pump

C: carrier protein/glucose permease/GLUT2

In the absorption of glucose into cells lining the villi within the ileum (small intestine), the glucose symporter (SGLT1) co-transports one glucose molecule into the cell for every two sodium ions it imports into the cell. The inward movement of sodium ions is assured by a sodium-potassium pump (powered by ATP) at the other end of the cell which reduces the internal concentration of sodium ions. Glucose (together with sodium ions) then diffuses out of the cell via a channel protein (GLUT2) - this is facilitated diffusion - and into a blood capillary on the outside of the cell.

What causes glucose to diffuse in this direction?
> Movement down a concentration gradient - glucose builds up in the cell as it is brought in by the symporter, and the flow in the capillary ensures a constant lower concentration at this end of the cell.
There are also a number of membrane-bound symporters that co-transport amino acids together with sodium ions into the epithelium lining the ileum.

Which of the structures (A, B and C) in the diagram opposite would also participate in the uptake of an amino acid?
> Only B - A and C would be specific for glucose

See the photomicrograph below showing brush border.

A different symporter (SGLT2) is also located in the proximal tubule in the kidney nephrons where it is responsible for the selective reabsorption of glucose into the blood.


Here the two substances move across the membrane in opposite directions.

The sodium-calcium ion exchanger or antiporter, which allows three sodium ions into the cell to transport one calcium out.

This is important in neurones and cardiac muscle cells as it acts quickly to reduce the cytoplasmic calcium concentration after activity.

[This is in fact additional to Plasma membrane Ca2+ ATPase (PMCA), which is a transport protein in the plasma membrane of all eukaryotic cells that also serves to maintain low concentrations of calcium (Ca2+) within the cells.]

Nitrate ion uptake from soil water and passage across the root

There are said to be 2 pathways though which water and solutes can pass between cells: the symplast - the cytoplasm within cells, where the enzyme nitrate reductase can convert nitrate ions to nitrite - and the apoplast - basically the inactive cell walls which provide a less selective route.

Nitrate ions (NO3-) enter the symplast (cytoplasm) of a root hair cell by means of an H+/NO3- symporter and remain in the symplast as they travel inwards from cell to cell toward the root xylem, moving by means of plasmodesmata - cytoplasmic strands linking cells directly. Once in the xylem, the NO3- ion travels upwards towards the leaf in the transpiration stream.

Uptake of nitrate is probably best seen as secondary active transport, and the activity is not confined to root hair cells, as the nitrate reductase activity creates a concentration gradient across the root.

Proton pumps

Within mitochondria and chloroplasts are a number of membrane-bound enzyme complexes that transport protons (hydrogen ions) across membranes, using energy from electrons. They thus build up an electrochemical gradient across the membrane and the protons accumulate within the space between membranes.
Protons pass back across the membrane via an enzyme ATP synthase resulting in the synthesis of ATP: ADP + Pi → ATP.

The ATP is used to power a number of metabolic processes inside cells, including active transport ...

Other proton pumps can be powered by ATP - which seems to doing the reverse of what goes on in mitochondria and chloroplasts. The plasma membrane H+-ATPase is used to drive secondary transport processes such as the uptake of metabolites. It creates electrochemical gradients in the plasma membrane of eukaryotes and also some prokaryotes.

In the stomach there is a proton pump - gastric hydrogen potassium ATPase (H+/K+ ATPase) - which acidifies the stomach contents and assists the working of the enzyme pepsin.

Adaptations for rapid transport across membranes

Membranes on the outside of cells may be modified to increase the efficiency of transfer of solutes across them. The exposed surfaces may be folded to increase the surface area. Additionally there can be an increase in the number of protein channels or carrier molecules embedded in the membranes - another aspect of the fluidity of the mosaic structure.

Plant root hair cells have fingerlike extensions of the cell wall (with a plasma membrane beneath), which increase their surface area to allow absorption of water and mineral ions from the surrounding soil.

Internal membranes within cells such as endoplasmic reticulum and Golgi body can also increase their surface area by folding. There are a number of membrane-bound enzymes ('permeases') which are used to import solutes into cells and mitochondria (by facilitated diffusion) which can be increased in number.

And of course both mitochondria and chloroplasts have inner folded sections which increase the surface area for carriers involving electron transfer.
microvilli1 (187K) Cells lining the small intestine, showing a brush border
(light microscope)
This sets the scene for the glucose/Na+ ion cotransport above. The membranes of the microvilli at the top of the cells are the location of SGLT1 - and capillaries containing red blood cells can be seen at the bottom - these carry away glucose and sodium ions.
microvilli4 (146K) Microvilli at the cell surface
Cells that are adapted for maximising the absorption of solutes often have intuckings - 'microvilli' - in their membranes. These show up as a 'brush border' in histological sections seen with the light microscope. This is well known in cells lining the ileum and colon, as well as in the kidney nephrons (proximal tubule, not the distal tubule).

Other related topics on this site

(also accessible from the drop-down menu above)

Similar level
Eukaryotic cells - more about the role of membranes in the internal organelles of plants and animals
Endosymbiont theory - more about the structure of mitochondria and chloroplasts as well as their evolutionary origins
Lipids - neutral fats and phospholipids, which membranes are made from
Proteins - which membrane channels are made from
Nerve cells, nerve impulses Big on membranes, sodium-potassium ion pumps, and all sorts of ion channels
Control of blood glucose concentration Quite a lot of substances crossing membranes
Control of blood water potential A few more substances crossing membranes
Respiration processes
The reactions of photosynthesis

Simpler level - but quite popular in its time
How substances get into and out of cells (osmosis)
Osmosis in operation in animal and plant cells

Interactive 3-D molecular graphic models on this site

(also accessible from the drop-down menu above)

The phospholipid molecule - rotatable in 3 dimensions
The phospholipid bilayer - rotatable in 3 dimensions
The cholesterol molecule - rotatable in 3 dimensions

Web references

Red cell membrane: past, present, and future Narla Mohandas and Patrick G. Gallagher

On bimolecular layers of lipoids on the chromocytes of the blood E. Gorter and F. Grendel

Aquaporin water channels: atomic structure molecular dynamics meet clinical medicine

Secondary Active Transport

Required practical: Investigation into the effect of a named variable on the permeability of cell-surface membranes.

Investigating the effect of temperature on plant cell membranes - From Nuffield Practical Biology

Membrane Permeability Beetroot Practical - YouTube video

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