Biomedical Engineering Reference
In-Depth Information
The central molecular event in the cell adhesion mechanics is the complex
binding and unbinding occurring between the receptors on the cell and the ligands
expressed on the endothelium during the rolling of the cell along the vessel
surface. The stochastic -calculus representation of formation and breakage of
a heterodimer complex between two molecules, Molecule1 and Molecule2, uses
both private and public channels (see Table
2
). The two molecules, represented by
two processes, share a public
bind
channel, on which one process (Molecule1) is
offering to send a message, and the other (Molecule2) is offering to receive. This
complementary communication abstracts the structural molecular complementarity
of the two molecules and the communication event represents the binding between
them. The private
backbone
channel, indicated with the scope operator ,issent
from Molecule1 to Molecule2; it represents the formed complex. After the com-
munication event the two Molecules change to a “bound” state (Molecule1 bound
and Molecule2 bound). A communication between the two “bound” processes on
the shared private channel
backbone
represents the complex breakage. As a result,
the two processes return to the initial “free” state (Molecule1 and Molecule2),
completing a full cycle. RA and RD are real numbers indicating the rates of
communication between the processes.
In these last years the stochastic -calculus has been used for modeling various
molecular systems, including transcriptional circuits, metabolic pathways and signal
transduction networks [
26
-
29
]. It has revealed its efficiency overall providing a
unifying view of both the molecular data and the dynamic behaviour it underlies.
Moreover, the stochastic -calculus simulated evolution of the various considered
biological system has been found to be in agreement either with the recent
experimental results or with the most consolidated theoretical models.
The developments of the experimental technologies,
1
occured at the end of
1990s, have allowed to better understand the molecular mechanism driving the
dynamics of lymphocyte interaction with vessels wall. The last studies based on
the intravital microscopy [
24
] have revealed that the process leading to lymphocyte
extravasation in inflammatory sites is a sequence of dynamical states (contact
with endothelium, rolling and firm adhesion), mediated by partially overlapped
interactions of different adhesion molecules and activation factors. On the basis
of these studies, the lymphocyte recruitment, can be efficiently modelled as a set
of concurrent processes. Furthermore, the BioSpi simulation of the time-evolution
of the molecular bonds density occurring during the dynamical interactions of the
rolling lymphocytes with the endothelium, can lead to predictive results about the
number of cells that undergo an efficient rolling and recruitment in inflamed vessels.
The stochastic -calculus may, thus, open new perspectives for the simulation of
this key phenomenon in the pathogenesis of autoimmune diseases, implicating not
only better knowledge, but also better future control of the autoimmune attack.
1
Major developments in the 1990s included experiments that provided direct measurements of
kinetic rates, lifetimes and detachment force of adhesive interactions.
