Biology Reference
In-Depth Information
membrane tethers. On the other hand, irm adhesion and transmigration of
leukocytes is mainly mediated by integrins, which have the interesting ability
to change their conformation and afinity state. It has been proposed that
under pathological conditions, leukocytes become activated and integrins
change from a bend conformation with low binding afinity to an extended
These changes in conformation and binding afinity allow the cell to arrest
and irmly adhere to the endothelium. During this process, the blood low
exerts dragging forces on leukocytes that, on the one hand, allow selectins
to dissociate at a certain rate necessary for rolling, while, on the other hand,
prevent integrins from irmly adhere unless they change their afinity state.
The adhesive capacity of cells depends not only on the adhesion strength
of individual CAMs, but also on other factors including the mechanical
properties of the cell, its activation state, the biochemical microenvironment
and the distribution and expression level of receptors and ligands.
1,2,13-15
However, to better understand cell adhesion, it is important to determine
the mechanism by which individual CAMs adhere and the effect that force
has on it. The most straightforward approach to study the adhesion strength
of single receptor-ligand interactions is by trying to answer the question:
What is the force required for breaking a bond?
This apparently simple
question has fundamental drawbacks both experimentally and theoretically.
In the following sections, we will try to describe the AFM as a model tool
to answer this question, the available approaches that have been applied
and the theoretical framework available to time to describe receptor-ligand
interactions.
11.2 NANOTECHNOLOGY TO STUDY CELL ADHESION
The study of molecules at the single-molecule level was not possible until
the development of adequate tools that provide positioning with nanometre
(nm) resolution and force application in the picoNewton (pN) to nanoNewton
(nN) range. During the last decades, many tools have been developed in this
direction, including magnetic and optical tweezers, the biomembrane force
probe or the AFM.
The AFM is probably the most widely used technique
given its versatility and applicability to many different ields, from pure
material sciences to cellular biology or surface chemistry. Indeed, the AFM
has been used for both imaging and manipulating biological systems at the
individual molecule level. In this section, we will describe its principle of
operation and its applicability to the measurement of binding strength of
receptor-ligand complexes.
16
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