In terms of permeability, water, dissolved gases such as carbon dioxide and oxygen and lipid solid molecules simply diffuse across the phospholipid bilayer because the fluidity permits them.

Water soluble anions (negative ions) generally pass through small horns less than .8 nm in diameter (.0000000008m; 1m=1000mm, 1mm=1000µ-micrometer, 1µm= 1000nm). However, all other larger molecules require carrier molecules or proteins to transport them through the membrane.


The following are an overview of the four different ways in which atoms and molecules cross the biomembrane, which is also called transmembrane transport:


  • Simple diffusion; is the process by which small molecules and ions simply, because of their tendency to spontaneously move around, especially from a region where they are highly concentrated towards a region where they are less, diffuse through the phospholipid bilayer of the biomembrane.


  • Facilitated diffusion; is the process by which, apart from water and ions, specific molecules such as monosaccharides and amino acids, diffuse through channel proteins down their concentration gradient. This assisted diffusion provides them with a special hydrophilic pathway since some molecules might resist the hydrophobic core of the phospholipid bilayer. Some specific ion channels remain open much of the time and are called nongated channels and others only open in response to specific chemical or electrical signals and referred to as gated channels, including the voltage-gated channels of the nervous system which transmit action potentials (nerve impulses) to the brain.


  • Active Transport; is the transmembrane transport that occurs when channel proteins, such as the enzyme ATPases (enzymes usually have the suffix –ase) use the energy of ATP hydrolysis (breaking one phosphate group from the nucleotide Adenosine triphosphate) to move ions or small molecules across a membrane against their chemical concentration gradient or electric potential gradient or both.


General Principle of ATP hydrolysis. Breaking bonds usually give off energy.


ATP-powered pumps which requires energy, is coupled to the hydrolysis of ATP and the overall reaction– ATP hydrolysis and the “uphill” movement of ions or small molecules- is energetically favorable. All ATP-powered pumps are transmembrane proteins with one or more binding sites for ATP located on the cytosolic face of the membrane.

Sodium/Potassium ATP Powered Pump.

Although these proteins commonly are called ATPases, they normally do not hydrolyze ATP into ADP and Pi unless ions or other molecules are simultaneously transported. Because of this tight coupling between ATP hydrolysis and transport, the energy stored in the phosphahydride bond (bond between two phosphate groups) is not dissipated but rather used to move ions or other molecules uphill against an electrochemical gradient.


  • Cotransporter; are also enzymes. They mediate coupled reactions in which an energetically unfavorable reaction, such as the movement of molecules or ions against their concentration gradient, is coupled to an energetically favorable reaction such as the passive transport of molecules down their concentration gradient. The co-transporter will use the energy of the passive movement to actively transport other molecules up their concentration gradient. Therefore, unlike ATP, two molecules have to always move through the co-transporter at one time.


This Cotransporter is a Symporter. More below. Click on image for credit.

 The co-transporter is sometimes referred to as secondary-active transporter because it uses the energy stored into an electrochemical gradient.

Cotransporters fall into two types:

1-            Antiporter: in which the movement of both molecules (energy favorable and unfavorable) are in opposite directions.

2-            Symporter: in which the movement of both molecules are in the same direction (see above image). This should not confuse you because the same principle applies- one molecule will be moving down its concentration gradient, and the energy in this will be used to actively move another molecule up its concentration gradient but in the same direction, similar to the Sodium/Potassium pump but without the need for ATP hydrolysis because the Cotransporters are smarter and more efficient than Active transporters or ATPases.


Membrane fluidity needs to be maintained for the cell to function normally, example, when red blood cells try to squeeze through blood capillaries. Also, fluidity allows small molecules to diffuse rapidly through and aids cell movement, growth, division etc.

Apart from temperature, one important factor for fluidity is the length of the hydrocarbon tail of the phospholipid in the bilayer which determines the stability and fluidity of the biomembrane. The longer the chain length of the tail, the more likely the hydrocarbon tails will interact with one another forming a secure and rigid structure.

Another factor is the degree of unsaturation of the hydrocarbon tail of the phospholipid in the bilayer. The chain that has a double bond does not have the maximum number of hydrogen atoms and the double bond creates a small kink in the hydrocarbon tail (chapter 2, lipids) which makes it more difficult for the tail to pack against one another and therefore more space for movement.

Additionally, certain types of movement within the membrane are more frequent than others;

Lipid Movement.

  1. Lateral Diffusion; molecules of the biomembrane simply transpose with neighboring molecules.
  2. Rotation; is when an individual lipid molecule rotates very quickly around its axis (up to 30’000 rotations per minute).
  3. Swing; from side-to-side.
  4. Flexion; contraction movement.
  5. Transverse Diffusion; also known as flip flop, is a movement of molecules from one half of a mono-layer to the other. The reason why flip flop happens less often is because the hydrophilic head of the lipid must go cross the internal hydrophobic sheet to go to the other mono-layer and faces a lot of friction. Flip flop is usually facilitated with the help of enzymes called flippases.

Because of flippases, different types of phospholipid molecules (Examples: Sphingomyelin, phosphatidylcholine, phosphatidylserine, phosphatidylethanol-amine, phosphatidylinositol and cholesterol) become concentrated in each monolayer making the bilayer asymmetrical. The two halves of the bilayer contain very different types of phospholipids and glucolipids, and the proteins of the bilayer have different orientations.

Example of asymmetry in the phospholipid bilayer of the biomembranes.

All these add up to create a highly diverse and fluid biomembrane.

3. Apart from membrane-lipids and membrane-proteins, the final basic component of a biomembrane is membrane-carbohydrates. However, they do not exist in isolation, rather in combination with membrane-lipids to form glucolipids/glycolipids, or combine with membrane-proteins to form glucoproteins/glycoproteins. The combination happens via covalent bonds.

Membrane-Lipids and -Proteins. Click on image for credit.

Most membrane carbohydrates are located on plasma membranes and have the following functions:

  • Improve the stability of membranes.
  • Advance the fastness and activate proteinase (protein enzymes which hydrolyze proteins into polypeptides) in the extracellular matrix.
  • Help membrane-proteins form correct three-dimensional configurations.
  • Take part in cell signal recognition, cell adhesion and cell junction (more detail later).
  • Correct the position and orientation of new proteins for transfer.
  • Lectin, a glucoprotein, protects the cell. So they also aid in protection.
  • Glucolipids act as blood groups determinants because some function as cell recognition particles.

I understand that stating these important roles is not enough to fully comprehend their significance. Later chapters will deal with the details. This is simply a fleeting reference to their roles.

In general, according to their main functions proteins and glycoproteins can be classified to five types:

  1. Channel proteins to form pores for the free transport of small molecules and ions across the membrane (more in Chapter 4).
  2. Carrier proteins to facilitate diffusion and active transport of molecules and ions across the membrane (more in next post).
  3. Cell Recognition Proteins; identifies a particular cell or gives them identity (more in Chapter 7).
  4. Receptor proteins; binds with specific molecules such as hormones and cytokines and gets activated to perform a specific function (also more in chapter 7).
  5. Enzymatic proteins; catalyze specific chemical reactions.
I think it is becoming clear that proteins are really important macro molecules and that most of animal cell biology will discuss it’s various functions.

Since the hydrophobic core is impermeable to many molecules, the presence of membrane-proteins helps to mediate the transport of specific molecules, ions and water across.

2. There are three forms in which a protein can link to a membrane:

  • Integral-membrane (Transmembrane) protein; is located in between the lipid bilayer (which is why it is called transmembrane). It has a region that faces inside of a cell called the cytoplasmic face or domain and a region facing outside of the cell called exoplasmic face or domain. The part of the protein that is in between the lipid membrane is called the transmembrane domain. Integral membrane proteins are also called Integrins for short. The transmembrane domain, unlike the other two domains, contain many hydrophobic amino acids whose side-chains interact with the hydrocarbon core of the phospholipid bilayer and form channels and cores that allow molecules to move into-and-out of the cell or organelle. A third title give to integrins because of this is Channel Proteins.

Three types of membrane proteins. Click on image for credit.

  • Peripheral membrane protein; partially penetrates the lipid bilayer (one leaflet) and sometimes even interacts with the integrin protein and can either be found on the cytoplasmic domain or the exoplasmic domain. It usually functions either as a receptor of signal molecules or as an enzyme.
  • Lipid anchored membranes; are covalently bound to one or more lipid molecules on the biomembrane surface. The hydrophobic carbon chain of the lipid, more specifically the leaflet, is responsible for the attachment and so it does not penetrate the phospholipid bilayer. It also functions similar to peripheral proteins.

All cells are surrounded by a layer of membrane that separates their internal environment (cytoplasm) from the external environment (exoplasm or extracellular matrix). Additionally, the organelles in cells, as explained earlier, are compartmentalized with the help of bio membranes, with similar chemical composition as that of the plasma membrane.

The membrane-enclosed organelles in the cytoplasm of cells (apart from the cell itself and the nucleus) are endoplasmic reticulum, Golgi apparatus, lysosome, vacuole, chloroplasts and mitochondria. So it is very important for us to understand the structure and chemical composition of the biomembranes.

Cell Structure. Click on Image for Credit.

Biomembranes are made of three types of macromolecules (one in each post :):

  1. The Lipid Bilayer which is largely made of phospholipid; (we’ve discussed earlier) a glycerol molecule is joined to two fatty acid chains and the third site on the glycerol is linked to a hydrophilic phosphate group. Phospholipids are therefore amphipathic lipids, meaning they are partly water soluble and partly insoluble. This is because they have both hydrophobic (fatty acid tail) and hydrophilic (phosphate group) regions.

Phospholipid. Click on Image for Credit.

In order to understand the lipid bilayer structure of a cell, hypothetically imagine its development- If we try to dissolve one phospholipid in a water molecule, the hydrophilic head (which contains the phosphate group) will dissolve in the water, whilst the hydrophobic tail will remain outside the water. However, if two or more phospholipids get together, they will start forming a different structure; the heads will still dissolve in water, but the tails, rather than facing outwards, will face inwards towards each other shielding the water out.

Lipid Bilayer Formation. Click on Image for Credit.

This molecular character causes phospholipids to form a spherically bilayer structure called liposome. In it, all nonpolar tails in each phospholipid molecular layer is called a leaflet. Examples of phospholipids are phosphatidylcholine (the phosphate group is attached to a second small hydrophilic compound such as choline. See first image) and sphingomyelin.

Because the lipid bilayer has a nonpolar hydrophobic core that is not easily permeable, biomembranes are interspersed or separated by proteins (referred to as membrane proteins) that allow certain molecules and ions to pass and so act as gateways or pathways towards and outwards the cell cytoplasm. The best analogy here is that of a concrete house interspersed with windows and doors to allow passage of people and air.

Fluid Mosaic Model. Click on Image For Credit.

Structurally, the plasma membrane is referred to as having a Fluid Mosaic Model. This refers to the story of Prophet Moses (Mosaic) parting the sea, and crossing over. The protein gateway here provide that effect.

Cholesterol is another lipid molecule that is present in the biomembrane. It consists of four hydrocarbon rings (that are strongly hydrophobic) and a hydroxyl group (O-H) attached to one end and is weakly hydrophilic. This quality makes cholesterol amphipathic as well.

One of its main functions is that it can break down the tight connection of the biomembrane phospholipid bilayer making it more flexible for the passage of small molecules and ions. Because of this and the fact that phospholipids have the capacity of movement within the biomembrane (more on this later), it explains the presence of “fluid” in the Fluid Mosaic Model.

In the electron microscope, the cell membrane appears to have a trilaminar appearance (having three layers):

Electron Microscopy of Plasma Membrane. Click on Image For Credit.

Two dark bands indicating the lipid bilayers of the hydrophobic tail and one bright band showing the intramembranous space between the bilayers. The hydrophilic core or polar head is not visible because it has dissolved in water.

A nucleic acid is a polymer made up of nucleotides.


Nucleotides are generally made of;

i. Nitrogen-containing base; a molecule which contains a nitrogen atom.

ii. Pentose sugar; meaning contains five carbon atoms in the sugar molecule.

iii. Phosphate Group; usually a phosphorus atom surrounded by a double bonded oxygen atom, single bonded to two oxygen negative ions and an oxygen atom.

A nucleotide.


Since the least complicated molecule is the phosphate group, it can easily be distinguished. However, for now, the distinguishing features for the nitrogen containing base will be the nitrogen atom and for the pentose sugar, the five carbon atoms. If the phosphate group is absent, the sugar-base combination is called a nucleoside.


The most common two forms of nucleotides are Ribonucleic acid (RNA) and Deoxyribonucleic acid (DNA), the molecules responsible for coding the proteins in the cell. (A complex procedure discussed in Chapter 8). The difference between the two is that the pentose sugar in DNA has one oxygen atom less. Also, since these two are the prime nucleic acids we shall be focusing on, their polymer structure is generally helical.


Difference between the DNA and RNA Pentose sugar.


Another popular nucleotide is Adenosine Triphosphate (ATP) which is used as an energy currency in the cell. This will be clearer in later chapters.

Adenosine Triphosphate.

            That is all for this chapter. Next, we begin a new chapter by successively describing every organelle in the cell and their function depending on how their molecules interact, now that you know the basics.

They are structurally important to the cell since they are the basic components of which the cytoskeleton is made, and functionally important since it is responsible for catalyzing reactions in the form of enzymes, have mobility functions, act as signal molecules for the cell and are part of a complex to form receptors for those signals and pretty much most other complicated functions. Due to these reasons, they are structurally complex as well.

Proteins are large polymers of amino acids joined together through peptide bonds to form polypeptides or in other words proteins. This is unclear unless you know what each bolded syllable is.

Amino Acid. Click on link for image credit

First, Amino Acids. Each amino acid consists of a central carbon atom bonded to a;

i-             Carboxylic-acid group (COOH); A carbon atom double-bonded to an oxygen atom and single bonded to a hydroxyl group (O-H).

ii-            Amino group (NH2); This is simply a nitrogen atom single bonded to two hydrogen atoms.

iii-           Hydrogen atom;

iv-           A distinctive side-chain that is unique to each type of amino acid, usually referred to as the “R” group. Thus, amino acids differ only in their side chains.

Amino acids get their name because of the amino group and the carboxylic acid group.

When two amino acids come close together, the hydroxyl group (OH) of the carboxylic-acid, which is polar, attracts a hydrogen atom of the amino group of the other amino acid and in the process, forms and releases a water molecule (See below image). This leads to the formation of a peptide bond which is a covalent bond between the carbon of the carboxylic-acid group of the first amino acid and the nitrogen of the amino group of the second amino acid. When many amino acids are linked together through peptide bonds, they form a polypeptide chain (or proteins).

Formation of a Peptide Bond. Click on image for credit.

Proteins are structurally complex. If you look at one (below), you can only see chaos. This is due to the fact that when amino acids begin to form peptide bonds with one another, they do not line up into a straight linear structure, rather, they begin to spiral and coil due to the interaction of their side chains with one another forming various types of (mostly) hydrogen and (sometimes) sulphur bonds.

Typical Protein. Click on image for credit.

So, in order to understand them, we theoretically unwind them and classify their structure under four different sections;

i-             Primary Structure; where we note the exact successive sequence of amino acids that make up the protein through the direct peptide links between them.

ii-            Secondary Structure; when the amino acids grow in number in the polypeptide chain, they begin to coil and either form an alpha helix (shown in diagram) or a beta-pleated sheet due to the indirect hydrogen links between the R-groups of the different amino acids. Here we discuss the amino acids which are forming those hydrogen links, usually four or five amino acids apart, and take the example of glycine (gly) below.

Protein structure. Click on image for credit.

iii-           Tertiary Structure; as the spiral itself coils and continue to spiral, the R-groups of amino acids from different locations (20 or 30 amino acids apart) in the chain will begin to interact and form hydrogen bonds.

 iv-           Quaternary Structure; here, two or more polypeptide chains will come close and interact with each other forming a dimer (two molecules), trimer (three molecules), tetramer (four molecules, as in above diagram) and so on.

This is a link to a very comprehensive video on youtube uploaded by user Pronerual which will delineate the concept of protein structure clearly.

The most distinguishing feature of lipids are the hydrocarbon chain, with a carboxyl group (C=O) at the end. This is the basic structure of lipids and called fatty acid. There are usually between 16-18 carbon atoms in the hydrocarbon chain.

In the diagram, the fatty acid is seen attached to a glycerol molecule and a phosphate group. It is known as a phospholipid. The carboxyl end of the fatty acid is highly polar and therefore water soluble (hydrophilic meaning attracted to water). Hydrocarbon chain of the fatty acid is highly non-polar and therefore water insoluble (hydrophobic, which means scared of water).

When fatty acids interact with water, the soluble carboxyl end dissolves and forms a layer with water, while the hydrocarbon tale remains outside the water surface. This quality is important in forming the bio membrane of cells which will become clearer in chapter 3.

Also, another quality to remember is when all carbon atoms of the hydrocarbon chain in the fatty acid are joined by a single bond, the compound is said to be saturated, this means that every carbon atom has hydrogen atom on both sides. In unsaturated fatty acid, one or more carbon atoms form a double bond with another carbon atom. Therefore, it will not be able to hold a hydrogen atom and therefore said to be unsaturated. As you can observe from the first diagram, there are two hydrocarbon tails, one is saturated and the other unsaturated and where the carbon atom forms a double bond, there can be seen a kink in the tail. This kink provides a fluid quality to cells that allows it more flexibility in motility and structure (more details in chapter 3) and therefore is healthier than saturated fats that plague processed food.

Usually fatty acids are stored in the form of triglycerides– glycerol molecule + 3 fatty-acid tails. A glycerol molecule plus a fatty-acid tail is a glyceride molecule. The diagram shows us a diglyceride consisting of two fatty-acids linked to a glycerol molecule. Triglycerides are insoluble in water and therefore group as fat droplets in the cytoplasm of the cell. When required, they can be broken down for use as energy.

Lipids provide an important form of energy storage, since they give more than twice as much energy as carbohydrates of the same mass. Also, as previously stated, they are the major components of cell membranes. Lastly, they play important roles in cell signaling. Example: steroid hormones, such as estrogen and testosterone are made of cholesterol and used in processing food and building nerve cells, apart from other metabolic functions.

Here we discuss the basic components or molecules that the cell is comprised of. This is more a Chemistry 101 lesson than anything else.

There are four classes of organic molecules in a cell, we’ll discuss one in each post.

Carbohydrates; As the name indicates, they consist of a Carbon atom (Carbo-) attached to a Hydrogen and an Oxygen atom in the ratio of 2:1, similar to water H2O (-hydrate from hydra in latin meaning water). They have a general chemical formula of (CH2O)n where n is usually any number ranging from 2 onwards.

The most popular carbohydrates have n= 3 (triose) or 5 (pentose) or 6 (hexose). Since most carbohydrates are sweet and sugary, sugar nomenclature end with “ose.”

They can be classified as single unit sugars which are called monosaccharides (mono means one, saccharide means sugar), or disaccharide (“di” means two therefore two unit sugars joined together), or oligosaccharides (3 to 50 unit sugars joined together) or polysaccharides (“poly” means many and it is above 50 units of sugar joined together). The bond that holds the saccharides together to form carbohydrates is called glycosidic bondand is formed by the loss of a water molecule when two carbohydrates come together and are subsequently joined by the oxygen atom of one of the two saccharides molecules.

Glycosidic bond being formed by the proximity of two monosaccharides.


Carbohydrates are usually used  as a food source since sugars are used to convert into energy (a process explained in detail in Chapter 5) . Example: Glucose (C6H12O6) is a monosaccharide or single unit sugar and is a common source of energy for the body. However, glucose is generally stored as an aggregated giant molecule starch in plants or glycogen in animals. They are polysaccharides or polymers (macromolecules). Actually “poly” means many, and “mer” means molecules therefore it means many molecules.

Three important disaccharides are maltose, lactose, and sucrose which are used as fodder to either make the storage macromolecules or to break-down into monosaccharides for converting the sugar into energy.


In addition to it’s role as energy storage, carbohydrates are also used in plant cell wall in the form of the polysaccharide cellulose to give the cell structure, and is an important signal receptor on the plasma membrane of cells where the signal will induce the cell to perform specific functions (more in chapter 7). This is done when oligosaccharides linked to proteins on the plasma membrane work as signal receptors or markers for cell recognition and interaction.

Next post, we’ll talk about fats!

Microscopes are important to visualize cells. The small size of cells makes the use of microscopes necessary; if two objects are close together; they start to look like one object. But if we can distinguish them, then it is said that we’ve resolved them. With normal human vision, the smallest objects that can be resolved is about 200 um (.2 mm in size).

The two most common types of microscopes are light microscopes and electron microscopes.

Light microscopes use light as a source of radiation and have a resolving power of .2 um (200 nm). This is one thousand times better than that of the human eye.

Electron microscopes, on the other hand, use electrons as a source of radiation instead of light. They also have magnets instead of glass lenses to focus an electron beam. The wave-length of an electron beam is far shorter than that of light. And the resulting image resolution is far greater. Also, a fluorescent screen resolution is .5 nm or 400 thousand times better than the human eye. However, in electron microscopes, cells have to be put in a vacuum in order to avoid the molecules in the cell to interact with the other gases in the atmosphere. The problem with this is that water boils in a vacuum at room temperature. Therefore, the cell needs to be dehydrated and killed. In addition, the components of the cell are colorless and need to be stained in order to view them.

Complicated right?

Also, there are two popular types of electron microscopes (EM) that provide different points of view of the cell; Scanning EM which provides a 3-dimensional view of the cell surface or topography and Transmission EM which provides an inside access into the components of a cell and it’s molecules.

I understand this is a short post but a very relevant one. This is all there is to the introduction, next post we’ll discuss the molecules of a cell.