Cell-cell adhesion represents the mechanism behind how cells interact with each other, based on molecule reactions at the surface of both cells. It is a crucial part of multicellular structural maintenance and, therefore, a foundation for multicellular organisms.
Cell-cell adhesion is controlled by cell adhesion molecules which recognize different ligands at cell junctions. Eukaryotes, prokaryotes and viruses have disparate cell adhesions molecules. For mammalian cells there are four main classes of cell adhesion molecule:
- Cadherins (calcium dependent glycoproteins)
- Integrins (transmembrane receptor proteins not dependent on calcium)
- Immunoglobin superfamily members (molecules involved in cell adhesion with an immunoglobin domain that are not dependent on calcium)
- Selectins (single-chained glyoproteins that are calcium dependent)
Anchoring junctions are the specific type of cell junction where cells attach to one another or to the extracellular matrix. They provide the structural cohesion necessary for tissue formation. There are three types of anchoring junction: desmosomes are a type of anchoring junction which connects cells to each other via cadherins, hemidesmosomes connect cells to the extracellular matrix via integrins, whereas adherens junctions form cell-cell and cell-matrix connections through both cadherins and intergrins.
Importance of cadherins for cell-cell adhesion
The calcium dependent cell adhesion molecules cadherins are usually 700-750 amino acids long. They are utilized in both desmosomes and adherens junctions to form protein complexes for cell-cell attachment. In desmosome complexes, a bridge is formed between the cadherins of each cell through homophilic binding.
This particular protein complex provides a strong adhesion useful for providing mechanical strength; therefore, desmosome complexes are abundant in heart and epidermis tissue that are frequently subjected to mechanical stress.
For adherens junctions, cadherins interact with actin filaments through intermediate anchor proteins called catenins. This type of cell-cell adhesion is common in epithelial and endothelial tissues.
Calcium has a pivotal role in cadherin functional activity by maintaining the rigid structure required for binding. In short, the calcium ions produce an inflexible structure through their positioning between each pair of cadherins, while the rigidity of the structure is positively correlated with the amount of calcium ions available.
Cell-cell recognition and cell-cell adhesion
Cell-cell recognition is an important part of the mechanism behind cell-cell adhesion. An early study noted the affinity found in cell adhesion molecules through the observation that cells from the same tissue preferentially adhere to one another. Cells disassociated from two separate organs can form a pellet when mixed, which gradually separate into cells derived from the same organ over time.
There are over one hundred different types of vertebrate cadherins and the experiment has been repeated with mixed cells sorted via cadherin type. It is these adhesive properties that allow for stable tissue architecture, albeit more recent assays have observed heterotypic binding affinity. It is believed that kinetic specificity allows cell adhesion molecules to recognize each other rather than broader thermodynamic specificity.
Selectins and cell-cell adhesion
Selectins are another type of calcium-dependent cell adhesion molecules that allow cell-cell interactions within the blood stream. Different types of selectin are utilized for white blood cells, blood platelets and endothelial cells.
The cell-cell adhesions within the bloodstream are formed through the selectin binding to a specific oligosaccharide on the adjacent cell. The binding of white blood cells to the endothelial cells lining blood vessels is particularly important in allowing the transportation of cells from the blood stream into tissues.
This cell-cell interaction between white blood cells and endothelial cells is strengthened by integrins, another cell adhesion molecule. The combination of selectins and integrins provides the weak adhesion that allows white blood cells to roll along the surface of the blood vessel. However, when necessary, the two cell adhesion molecules can also bind the blood cell strongly to the endothelial cell surface for exit through the blood vessel between endothelial cells.
Reviewed by: Dr Tomislav Meštrović, MD, PhD