A practical cell density stabilization technique through drug infusions: a simple pathfinding approach

Abstract

We consider a nonlinear system with distributed delays modeling cell population dynamics, where the parameters depend on growth-factor concentrations. A change in one of the growth factor concentrations may lead to a switch in the corresponding model parameter. Our first objective is to achieve a network representation of the switching system involving nodes and edges. Each node stands for a full-fledged nonlinear system with distributed delays where the parameters are constant. For each node, a stable positive steady state may exist. In the network framework, a change in the growth-factor concentration is interpreted as a transition from one node to another. The objective is then to determine the best switching signal steering the biological parameters over time, making the overall dynamic system moving from one operating mode to another, until reaching a desired stable state. Our method provides a (sub)optimal therapeutic strategy, guiding the density of cells from an abnormal state towards a healthy one, through multiple drug infusions. The drug sequence is deduced from the optimal switching signal provided by a classical pathfinding algorithm, associated with the network representation.