Modeling the molecular network controlling adhesion between human endothelial cells: Inference and simulation using constraint logic programming

Abstract

Cell-cell adhesion plays a critical role in the formation of tissues and organs. Adhesion between endothelial cells is also involved in the control of leukocyte migration across the endothelium of blood vessels. The most important players in this process are probably identified and the overall organization of the biochemical network can be drawn, but knowledge about connectivity is still incomplete, and the numerical values of kinetic parameters are unknown. This calls for qualitative modeling methods. Our aim in this paper is twofold: (i) to integrate in a unified model the biochemical network and the genetic circuitry. For this purpose we transform our system into a system of piecewise linear differential equations and then use Thomas theory of discrete networks, (ii) to show how constraints can be used to infer ranges of parameter values from observations and, with the same model, perform qualitative simulations. © Springer-Verlag Berlin Heidelberg 2005.