Surface Modification of Epithelial Cell Membrane and Trans-Epithelial Potential

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Image: Illustration of tight junction, gap junction, and Desmosomal junction (desmosome), by Boumphreyfr. License: CC BY-SA 3.0

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Types of Epithelium

There are three basic types of epithelial cells. Each of these types is further categorized into simple (if it is a single layer of cells) or stratified (if the cells are arranged in multiple layers).

The squamous epithelium is made up of flattened cells. The simple squamous epithelium is present in areas of the body where diffusion, absorption, or filtration takes place, as the flattened structure of the cells decreases the diffusion pathway. The stratified squamous epithelium being multilayered protects the organs from mechanical or chemical insult.

The cuboidal epithelium is made up of cuboid-shaped cells with a central nucleus. They are present in the areas of the body where secretory function is required, such as the pancreatic ducts. The columnar epithelium consists of elongated cells. These cells may have cilia present on their surface and form pseudostratified ciliated columnar epithelium. The cilia entrap particles and move them toward the external orifice, e.g., ciliated columnar epithelium in the airways.

Surfaces of Epithelial Cells

An epithelial cell typically has four surfaces:

• The apical surface, which faces the lumen; also known as the ‘luminal border’
• The two lateral surfaces, through which one epithelial cell communicates with the epithelial cells on each side
• The basolateral surface, which is opposite to the apical surface and faces the basement membrane

Modification of Epithelial Cells

Cilia, villi, and microvilli

As mentioned above, the cilia are present on the columnar epithelium and produce a to-and-from motion to entrap the particles and move them in a specific direction parallel to the surface of the epithelium. Therefore, they are, in addition to other mechanical barriers, included in the primary defense of the body. The villi and microvilli are present on the absorptive surfaces as they increase the surface area for absorption without increasing the size of the epithelium.

Channel proteins and carrier proteins

In order to move molecules from the lumen into the cells and from cells into the blood or vice versa, channel proteins and carrier proteins are present on the apical and basolateral surfaces of the epithelial cells.

The channel proteins allow small ions to move across the cell membrane. These are often gated to open and close in response to a certain stimulus.

Carrier proteins move large molecules across the cell membrane. If the molecules are moved against the concentration gradient, these carrier proteins use an ATP molecule. They can carry two or more molecules at a time. When these molecules travel in the same direction, the action is called ‘cotransport’; when they move in opposite directions, it is called ‘countertransport.’

Sodium–potassium (Na-K) pump

The Na-K pump is a carrier protein that moves three Na ions out of and two K ions into the cell against the concentration gradient. An ATP molecule is broken to give the energy required for the transport of ions.

Aquaporins

Aquaporins are specialized channel proteins present on the apical and basolateral surfaces of epithelial cells. These are present in areas where excessive water reabsorption is required, e.g., the collecting duct of a nephron. Aquaporins allow the transcellular flow of water molecules.

Epithelial cell junctions

A cell junction is a multiprotein complex that provides contact between neighboring cells or between the cell and the extracellular matrix. There are four types of cell junctions present in an epithelial cell: tight junctions, gap junctions, anchoring junctions, and adhering junctions.

Tight junctions

Tight junctions act as a barrier to regulate the movement of molecules from one cell to another through extracellular spaces by diffusion or active transport. They are present on the lateral surfaces of the epithelial cells. They can be tighter with high electrical resistance or leakier with low electrical resistance.

Gap junctions

Gap junctions are also known as ‘communicating junctions.’ They allow the cytoplasmic connection between two neighboring cells without the involvement of extracellular fluid. The connexin proteins form a cylindrical structure between the lateral surfaces of two adjacent epithelial cells. This cylindrical structure with pores is called the ‘connexon.’ Its main role is to allow free movement between the cells of ions and small molecules.

Anchoring junctions

Anchoring junctions are made of anchoring proteins, which link the cytoskeleton of one cell to the cytoskeleton of another cell or to the extracellular matrix. The adhering junctions and desmosomes are present on the lateral surface of two epithelial cells, while the hemidesmosomes are present on the basolateral surfaces.

Adhering junctions

Adhering junctions consist of actin and cadherin protein filaments. Because actin is a contractile protein, the adhering junctions are also responsible for the change in the shape of sheets of the cells. These junctions are meant to hold epithelial cells together.

Desmosomes are made of intermediate filaments composed of keratin and desmin. Cadherin acts as a transmembrane linker. Desmosomes are specialized to hold cells tightly together.

Hemidesmosomes form a bridge between the epithelial cells and the extracellular matrix on the basolateral surface. They have intermediate filaments as the cytoskeletal anchor and integrin as the transmembrane linker.

Transepithelial Transport

Transepithelial transport is the transport of a molecule from the lumen into the blood. In this case, the molecule, which needs to be absorbed, has to travel through more than one membrane surface.

Therefore, the transepithelial membrane potential difference is measured. This is the voltage across the epithelium and the sum of the membrane potentials for the outer and inner cell membranes.

Transepithelial transport is also a useful tool for the diagnosis of cystic fibrosis, in which the transepithelial membrane potential is more negative. In cystic fibrosis, the impaired cystic fibrosis transmembrane regulator (CFTR) causes the increased secretion of chloride (Cl) ions into the lumen and the increased reabsorption of Na ions into the epithelial cells. This results in thick mucus secretions.