Biomedical Engineering Reference
In-Depth Information
1
Introduction
The biophysics of cell adhesion is the most intensively investigated area of
cell mechanics. These studies have been driven by the strong interest in many
biological processes of which cell adhesion is an important element, leading to
the development of a number of mathematical models. Cell attachment to and
detachment from a surface, such as, for example, endothelial surface that lines the
blood vessel wall is a central aspect in the inflammatory processes.
The lymphocytes are the cells whose adhesion mechanical properties are most
deeply studied, because of their central role in the tissues response to inflamma-
tion. Lymphocyte adhesion under blood flow in microvasculature is mediated by
binding between cell surface receptor and complementary ligands expressed on the
endothelium, the surface lining the blood vessel wall. Lymphocyte adhere to the
endothelium in a 4-phases mechanism: tethering and rolling (primarly mediated
by selectins and in part also by integrins), firm adhesion (primarly mediated
by integrins) and finally the cell migration through the endothelium toward the
inflammation site. The rolling along the walls of vessels enables the lymphocytes
to survey the endothelial surface for chemotactic signals, that stimulate their arrest
and migration through the endothelium and its supporting basement membrane.
This kind of mechanism is a critical event in the origin and evolution of the
autoimmune diseases. In the ambit of this kind of pathologies, we mention the
multiple sclerosis, an inflammatory disease of the central nervous system. A novel
intravital microscopy model to directly visualize and analyze through the skull the
interactions between lymphocytes and endothelium in celebral venules of mice
has been created [
24
]. This technique allows to characterize each step and each
species of adhesion molecules implicated in the lymphocytes recruitment in brain
vessels. A realistic quantitative model and simulation
in silico
of the process
leading to the extravasation of the lymphocyte from the blood vessels into the brain
tissue may permit quantitative predications and subsequently a better control of the
autoimmune attacks.
The most common approaches to the simulation of cell rolling process can be
classified into three categories: mechanical, thermodynamic and kinetic. Mechanical
models describe the lymphocyte rolling as peeling of a flexible and inextensible
tape. The dynamics is formalized resorting the concept of adhesion energy. Analysis
based on the energy conservation allows adhesion energy to be related to the work
done by external forces and the energy stored in and dissipated by the deformed cell
[
10
,
18
,
30
]. Thermodynamic models were developed concurrently to mechanical
ones, in order to relate the adhesion energy to physicochemical properties of
adhesive receptors and their interactions [
3
,
31
].
The major result of the thermodynamical treatment is the expression of the
adhesion energy in term of the number of bonds in the contact area. The adhesion
energy density was found to be directly proportional to the number of molecular
bonds between receptors and ligands and inversely proportional to the K
B
T ,where
K
B
is the Boltzmann constant and T the absolute temperature.
