Biomedical Engineering Reference
In-Depth Information
3.
Integrin-ligand interaction
. The interaction between the active form of inte-
grins (˛
4
on lymphocyte, the correspondent receptor VCAM-1 on endothelium;
LFA-1 on lymphocyte and its receptor ICAM-1 on endothelium) causes the firm
adhesion of the cell. It has also a less relevant role in rolling process.
We describe the implementative choices effected to model each of these molec-
ular reactions and the subsequent kinetic state of the cell adhesion.
Selectin-lingand interaction
Rolling is a state of dynamic equilibrium in which
there is rapid breaking of bonds at the trailing edges of the lymphocyte-endothelium
contact zone, matched by rapid formation of new bonds at the leading edge. To
represent the formation and the breakage of a complex between the two molecules
PSGL-1 and P-Selectin we use both public and private channels. Each of the
molecules is represented by a process (PSGL1 and PSELECTIN in Table
3
). The
two processes share a public
bind
channel, on which one process, PSGL1) is
offering to send a message, and the other, P-SELECTIN is offering to receive. These
complementary communication represent the complementarity of the two molecular
domanins involved in the bond formation. The communication event represents
the binding. The private channel
backbone
offerend by the binding site of PSGL1
molecule (BINDING PSITE process) is sent from PSGL1 to PSELECTIN and rep-
resent the formed complex. After the communication event the two molecule change
to a “bound” state PSGL1 BOUND and PSELECTIN BOUND. A communication
between the two bound processes on the shared private
backbone
channel represents
complex breakage. As a result, the two processes return to the “free” state (PSGL1
and PSELECTIN).
Integrinic activation by chemokines
Integrins undergo dynamic functional
changes, generically referred as “activation”, which increase the ability of cells to
interact with entracellular ligands. Their activation is a consequence of the binding
of different kinds of chemokines with their receptors that generates both pro- and
anti-adhesive intracellular signaling events, that are relevant to the kinetic adhesion
and de-adhesion and to cell movement during diapedesis. However, because our
implementation focus on the simulation of the kinetics of the lymphocyte, we
model the integrinic activation by chemokines as a change of state of the integrinic
molecules subsequtn to the binding of a generic chemokines species with its
receptors. A process CHEMOKINE, representing the chemokine molecule offers a
private channel
chemobb
on its binding domain BINDING CSITE. The chemokine
receptor, represented by the process CHEMOKINE REC shares with the process
CHEMOKINE the public channel
lig
, on which CHEMOKINE sends a message
(the name
chemobb
) and CHEMOKINE REC receives it. After communication
CHEMOKIN change to a bound state CHEMIKINE BOUND, that consists of the
parallel composition of three processes ACT1, ACT2 and ACT3. The first two
processes represent the activation of ALPHA4 and LFA1 integrins molecules
and the third represent the breakage of the complex CHEMOKIN BOUND.
ACT1 and ACT2 processes send, with a communication rate A, the names
sign1
and
sign2
on the global channels
alpha act
and
lfa act
respectively.. After the
communication the processes ACT1 and ACT2 don't change state. The process
