Biomedical Engineering Reference
In-Depth Information
A Process-Algebra Model of the Cell Mechanics
of Autoreactive Lymphocytes Recruitment
Paola Lecca
Abstract
Lymphocytes roll along the walls of vessels to survey the endothelial
surface for chemotactic inflammatory signals, which stimulate the lymphocytes
to stop rolling and migrate through the endothelium and its supporting basement
membrane. Recent studies about the inflammatory process of the brain leading to
the multiple sclerosis, have revealed that lymphocytes extravasation 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. These interactions are both concurrent and parallel, and consequently their
modelling need to be specified in a language able to represent concurrency and
parallelism.
Process calculi (or process algebras) are a diverse family of related languages
developed by in computer science for formally modelling concurrent systems. Here,
we propose the use of the biochemical stochastic -calculus. This calculus is an
efficient tool for describing the concurrency of the different interactions driving
the phases of lymphocytes recruitment. It models a biochemical systems as a set
of concurrent processes selected according to a suitable probability distribution
to quantitatively describe the rates and the times at which the reactions occur.
We use here this tool to model and simulate the molecular mechanisms involved
in encephalitogenic lymphocytes recruitment. In particular, we show that the
model predicts the percentage of lymphocytes involved in the rolling process on
the endothelium of vessels of different diameters and the adhesion probability of
the cell as function of interaction time. The results of the model reproduce, within
the estimated experimental errors, the functional behavior of the data obtained from
laboratory measurements.
P. Lecca (
)
The Microsoft Research, University of Trento, CoSBi, Trento, Italy
e-mail:
lecca@cosbi.eu
