Passive Diffusion Vs Active Transport

Examples and Differences

Passive diffusion and active transport are modes of transfer through which substances (ions, water, and other molecules, etc) move in and out of the cell through the cell membrane. Although they are both involved in the movement of substances through the membrane, the mechanism through which movement is achieved is different between the two. 

Passive diffusion is a type of diffusion characterized by the movement of substances in the direction of the concentration gradient without any energy input. Basically from an area of higher concentration to an area of lower concentration.

The following are a few examples of passive diffusion: 


Passive Diffusion Examples


One of the best examples of passive diffusion is osmosis. Essentially, osmosis refers to the movement of a solvent (e.g. water) from an area of low solute concentration to the area of higher solute concentration through a membrane.

In a biological system, a semipermeable membrane separates the extracellular matrix from the cytoplasm. Here, the concentration of solutes within the cell, as well as in the extracellular matrix surrounding the cell, determines the direction in which the solvent moves. 


Fig. 1 


* The arrows in fig. 1 represent direction of the solvent (water)



Using the diagram above as an example, it's possible to see how a higher concentration of solutes (represented by large red dots) on one side of the membrane influence the movement of the solvent.

Generally, the osmotic potential of pure water is zero. However, when solutes (e.g. sodium ions) are added, the osmotic potential of water is reduced and becomes slightly negative.

If the solutes cannot pass through the membrane (diffusion), then the water is forced to move from the area of higher osmotic potential  to the area of lower osmotic potential of water.

In fig. 1, there are more solutes on the right side of the membrane compared to the left side.

For this reason, the solvent on the right side of the membrane has a low osmotic potential compared to the solvent on the left side. Due to this osmotic gradient, water molecules are forced to move from the area of higher osmotic potential to the side with lower osmotic potential.  


* In plants and animals, as well as microorganisms, osmosis is an important mechanism through which cells take up water. In the process, the bulk flow of water also aids in the transportation of small, dissolved solutes and nutrients into the cell (e.g. in plant roots). 

In animals, the mechanism also plays an important role in water retention. For instance, through osmosis, fluid is transported from the kidney tubules and gastrointestinal tract and into the capillaries. This process prevents excessive amounts of water from being excreted along with urine. 

As mentioned, water molecules easily pass through the cell membrane through osmosis. Being a form of passive diffusion, this mechanism does not require any energy input nor does it heavily rely on integral proteins involved in the transport of ions and larger polar molecules. 

Here, however, it's worth noting that water molecules have a polarity which would affect their movement across the phospholipid bilayer which has a hydrophobic region. As compared to other polar molecules, water molecules are small in size which allows them to easily pass through the lipid layer. 

In vitro as well as in vivo, the relative concentration of dissolved solutes (in a solution or in the extracellular matrix) has a direct influence on the direction as well as the rate at which water will move in or out of the cell. 

In a hypotonic solution, water enters the cell given that the solution or extracellular fluid has a lower osmolarity compared to the cytoplasm. Essentially, this means that the cytoplasm has a higher concentration of solutes compared to the extracellular matrix or solution. An isotonic solution, on the other hand, has the same osmolarity as the cell. 

In this scenario, there is no osmotic gradient to influence a net movement of water in or out of the cell. Rather, water molecules move in and out of the cell at nearly the same rate.  Lastly, in a hypertonic solution (or extracellular fluid with hypertonic conditions), the high osmolarity conditions outside the cell force water molecules to leave the cell - As a result, cells start to shrink. 

For example, in a case where soil contains a very high concentration of salt (compared to the concentration of salt in the root cells of a plant), water is forced to move from the root cells. As a result, the plant gradually wilts and eventually dies. 


* Although water can pass through the lipid bilayer, it's also transported through channels known as aquaporin channels.

Generally, the factors that influence the movement of water in or out of the cell include:


  • Size of the water molecules
  • Osmotic gradient 


Simple Diffusion

Simple diffusion is also a type of passive diffusion. Here, a good example of simple diffusion is the movement of small lipophilic molecules through the cell membrane. 

Essentially, lipophilic molecules include molecules capable of dissolving in lipids, fats, steroid hormones, and various non-polar solvents.  In addition to being lipophilic (lipid loving), these molecules are also nonpolar. As such, they are able to easily diffuse through the membrane in the event of a concentration gradient. 

This type of movement has also proved effective for the transportation of lipophilic drugs. Given that some of the drugs tend to be weak organic acids or bases that exist in an un-ionized form, they are able to easily diffuse through the cell membrane to enter the cell. 

In addition to being un-ionized and lipid-soluble, the concentration gradient (high concentration of molecules outside the cell compared to inside the cell) forces these molecules to move into the cell with ease. 

Here, studies have shown smaller molecules of the drug to penetrate the membrane more rapidly compared to the larger ones. This being an example of passive diffusion, no energy is used to transport the molecules across the cell membrane. 


In summary, some of the factors that influence the movement of these lipophilic molecules across the cell membrane include:


  • Size of the molecule
  • Ionization state - Ionized molecules have low solubility 
  • Being lipophilic 
  • Concentration gradient 


* Facilitated diffusion is also regarded as a type of passive diffusion. While it does not require energy (similar to the other types of passive diffusion), facilitated diffusion is dependent on transmembrane integral proteins located on the cell membrane for transportation of substances in or out of the cell down their concentration gradient. 


Active Transport

Unlike passive diffusion (and even facilitated diffusion) where molecules move down a concentration gradient, active transport involves the movement of molecules against the concentration gradient. 

This, therefore, means that molecules have to be moved from an area of low concentration of the molecules to an area where they are highly concentrated. As such, active transport can be said to prevent diffusion given that it prevents molecules or ions from moving down their concentration gradient. 

For instance, in neurons, active transport prevents sodium and potassium ions from moving down their concentration gradient thus propagating the action potential (electrical signal). 


There are two main types of active transport that include:


· Primary active transport - This type of active transport involves the use of ATP energy to move molecules against their concentration gradient. 

· Secondary active transport - Unlike the primary active transport, secondary active transport uses electrochemical energy to transport ions 


Active Transport Examples

Transport of Calcium Ions out of the Cell

In general, the concentration of calcium ions in the cells is significantly low compared to the concentration of these ions outside the cell. Concentration of calcium ions is about 1000 times more than inside the cells. This is evidence that the cell is constantly pumping out calcium ions out of the cell thus moving calcium ions against their concentration gradient. 

This is particularly important as it prevents the accumulation of calcium phosphate crystals that would otherwise kill the cell. Calcium phosphate crystals may form following a reaction between calcium ions and ATP molecules.

Increased entry of calcium ions into the cell (through the calcium ion channels) may carry a signal thus causing changes within the cell. 

For this reason, calcium ions have to be pumped out. To do this, ATP energy is required to not only close the cytosolic gate and open the extracellular gate but also cause a conformational change of the pump proteins that bind to the calcium ions during transportation. 

The following is a diagrammatic representation of this mode of transportation:

Fig. 2



In figure 2, the calcium ion in the cytoplasm fast binds with the cytosolic gate of the calcium pump causing it to open. At this point, the pump proteins have a high affinity for calcium and thus allow the calcium ions to enter/attach.

In the next step, hydrolysis of ATP at the calcium pump causes the cytosolic gate to close and the extracellular gate to open. In addition, it influences conformation change of the proteins which changes their affinity for calcium ions.

As a result, the calcium ions are released into the extracellular matrix. Given that the proteins have no affinity for calcium ions, the calcium ions in the extracellular matrix cannot bind to the pump proteins to be transported into the cell. 


* Unlike calcium channels (also known as voltage-gated calcium channels), calcium pumps only transport calcium ions out of the cell against their concentration gradient.


* Following hydrolysis of ATP, a phosphate from the ATP will attach to the pump protein causing a conformational change.


* During the active transportation of sodium and potassium ions through the sodium-potassium pump, ATP is required. Here, hydrolysis of ATP allows for three (3) sodium ions to be transported out of the cell through the sodium-potassium pump and two (2) potassium ions to be transported into the cell. 

By attaching/binding to the pump proteins, the phosphate from ATP increases affinity for sodium ions allowing them to be transported out.

When the phosphate separates from the proteins, they undergo conformation change which causes them to lose affinity for sodium ions and increase affinity for potassium ions. This allows for potassium ions to then be transported into the cell. 


Vesicular Transport


Vesicular transport is also an example of active transport. This mode of transport is concerned with the transportation of macromolecules across the plasma membrane.

For instance, the transportation of these molecules outside the cell (e.g. transportation of hormones by endocrine glands out of the cells) is known as exocytosis while the intake of macromolecules across the cell membrane is known as endocytosis (phagocytosis or pinocytosis).

In phagocytosis, studies have shown the absence of or reduced ATP to negatively affect the ingestion of macromolecules. However, the availability of extracellular ATP has been shown to play an important role in the transportation of calcium ions and thus the invagination of the membrane to create a vesicle in which macromolecules are taken into the cell. Therefore, active transportation in this case requires the use of energy. 


Some of the other examples of active transport include:


  • Transportation of amino acids into the cells of the intestinal lining 
  • Pinocytosis
  • Transport of some sugars against their concentration gradient 


Both passive diffusion and active transport are methods through which substances (molecules, ions, macromolecules, etc) are transported into or out of the cell (or across a membrane).

They are important mechanisms that ensure that various material required by the cell is successfully transported into the cell and that some substances (e.g. waste material or substances secreted in the cell) are removed from the intracellular environment.

While the two have the same functions, the manner in which this is achieved varies in a number of ways. The following are some of the main differences between the two mechanisms of transportation. 


Passive Diffusion is dependent on the Concentration Gradient


One of the main differences between passive diffusion and active transport is the fact that passive diffusion involves the movement of substances down their concentration gradient. This simply means that substances will move from where they are highly concentrated to where they are less concentrated. 

In active transport, substances are transported against their concentration gradient. This means that substances will be actively transported from where they are less concentrated to the area in which they are highly concentrated. For this reason, energy is required. 

This is different from passive diffusion in that the concentration gradient forces the highly concentrated molecules to move towards the area where they are highly concentrated. 


* While concentration gradient plays an important role in passive diffusion, the the size and polarity of the molecules also directly impact this mode of transportation particularly in biological systems. 

For instance, while very small molecules can easily diffuse through the cell membrane, other small substances like ionic substances would not easily pass through the membrane and thus have to be actively transported. 


Active Transport requires Energy

As mentioned, active transport plays an important role in moving substances against their concentration gradient. This means that it's involved in moving substances from an area in which they are less concentrated to an area in which they are highly concentrated. To do this, active transport uses energy. 

In addition to energy requirements, active transport is also dependent on transmembrane integral proteins that act as transporters. Unlike passive diffusion, where a concentration gradient as well as the size and polarity of molecules, influence movement of substances through the membrane, the concentration gradient actually acts against active transport. It's for this reason that energy has to be spent to move substances against the gradient.

Although ATP (adenosine triphosphate) is one of the most common forms of chemical energy, it is not directly involved in all forms of active transport. For this reason, active transport is divided into two main categories that include primary and secondary active transport. 

In primary active transport, direct hydrolysis of an ATP molecule results in the production of a phosphate that causes a conformational change of the transporter proteins thereby promoting the transport of given substances (e.g. ions). In this case, then, ATP is required for the protein transporters to function as required. 

Secondary active transport (also referred to as Co-transport) does not directly depend on ATP energy. Rather, it's dependent on the electrochemical gradient created during primary active transport through which ions were pumped out of the cell against their concentration gradient. 

By actively pumping out ions (e.g. sodium ions), there is an increased concentration of these ions out of the cell. As a result, an electrochemical gradient increases in the extracellular fluid surrounding the cell. 

As a result of this gradient, these ions are forced to move down their concentration gradient into the cell through the protein transporters. However, because of their charge, they also bind to other substances (e.g. glucose molecules) and thus help transport them into the cell.

Here, then, secondary active transport is dependent on the electrochemical gradient that resulted from primary active transport. 


* Although facilitated transport requires protein transporters to move substances down their concentration gradient, energy is not used.


Active transport is involved in the Transport of relatively larger Substances

As already mentioned, smaller non-polar molecules as well as lipophilic molecules (e.g. oxygen and carbon dioxide, etc) can easily diffuse through the lipid bilayer to enter the cell. Because of their small size, they can easily pass through.

Larger molecules, particularly macromolecules, cannot easily diffuse through. For this reason, a good number of these molecules depend on active transport to move them through the membrane against their concentration gradient. 


* Some of the larger are transported through integral proteins down their concentration gradient - facilitated diffusion and thus no energy is used.


Active Transport moves substances in one direction

Because of the manner in which active transport works, substances are only transported in one direction. As previously mentioned, this type of transport serves to move substances against their concentration gradient.

Energy is required to ensure that substances like ions are moved in a specific direction (e.g. out of the cell). Here, opening and closing of the cytosolic gate and extracellular gate of the ion pumps ensures that ions are not allowed to pass through in the opposite direction once they have been transported across the membrane.

In passive diffusion, channels allow substances to move in any given direction as long as there is a concentration gradient. As well, substances can slowly disperse in and out of the cell by diffusing in the lipid bilayer if there is a concentration gradient. 

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Alexey V. Melkikh and Vladimir D. Seleznev. (2012). Mechanisms and models of the active transport of ions and the transformationof energy in intracellular compartments.  

N A Abumrad, Z Sfeir, M A Connelly, and C Coburn. (2000). Lipid transporters: membrane transport systems for cholesterol and fatty acids.

Ruchi Gaur, Lallan Mishra and Susanta K. Sen Gupta. (2014). Diffusion and Transport of Molecules In Living Cells. 

Yip-Wah Chung. (2006). Introduction to Materials Science and Engineering.  



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