Biology Reference
In-Depth Information
The biological bonds between CAMs are noncovalent bonds that
generate strong, speciic interaction between two molecules. Speciicity is
accomplished by the complementary geometry of the interacting molecules
that favours force cooperation.
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Unlike covalent bonds, which are strong and
can be broken only by expending a signiicant amount of energy, the weaker
receptor-ligand interactions that can rupture by spending one single ATP
molecule are mediated by a combination of noncovalent interactions (van der
Waals, electrostatic, etc.) and are normally described by an intrinsic lifetime
or afinity constant.
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In tissues, cells adhere to each other and to the extracellular matrix
forming adhesion complexes, such as focal adhesions, adherens junctions and
gap junctions. Different types of proteins are responsible for the formation
of these complexes, including, among many other, integrins, cadherins and
connexins.
1,2
Even if the binding process is dynamic in nature, integrins and
cadherins, for example, have long effective lifetimes, as they are known to
form clusters, which also allow for the rapid rebinding of a protein, when
occasionally dissociates. This permanent contact enables cells to form tissues
creating barriers that restrict the passage of luids, macromolecules and
other cells. In addition, these types of adhesion complexes provide structural
integrity and speciicity to different tissues. Structural integrity is provided
by the connection of CAMs to the cytoskeleton through complex structures
composed by various proteins.
1,2
For example, focal adhesions are formed
by the adhesion molecule integrin, which tethers the cell to the extracellular
matrix, while the cytoplasmic region binds to talin and other proteins that
connect it to the actin cytoskeleton. Speciicity is accomplished by expressing
particular types of CAMs that recognize speciic ligands. In the case of the
cadherin superfamily, which mainly mediates cell-cell adhesion, there are
different subtypes that are characteristic of speciic tissues. Most tissues
are constantly subjected to mechanical stress. For example, lung and cardiac
tissues are cyclically stretched because of breathing and heart beating,
respectively. This involves that cell adhesion complexes are subjected to
mechanical force. Then, their adhesion strength has to be strong enough to
support these cyclic forces.
The leukocyte adhesion cascade provides the most relevant example of
dynamic adhesion. Leukocytes (white blood cells) travel with the bloodstream
without irmly adhering to the vascular tissue but patrolling it in search of
signals of injury or inlammation.
3
Under pathological conditions, the cell
passes through states of rolling, irm adhesion and transmigration. These
steps involve different types of adhesion molecules with varying binding
afinities. Rolling is mainly mediated by selectins and some types of integrins
that are weakly linked to the cytoskeleton and allow the formation of long
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