A model of cellular decision making in photodynamic therapy of cancer

Abstract

The aim of this report is to provide a mathematical model of the mechanism for making binary fate decisions about cell death or survival, during and after type II photodynamic therapy (PDT) treatment, and to supply the logical design for this decision mechanism as an application of rate distortion theory to the biochemical processing of information by the physical system of a cell. Based on system biology models of the molecular interactions involved in the PDT processes previously established, and regarding a cellular decision-making system as a noisy communication channel, we use rate distortion theory to design a time dependent three dimensional Blahut-Arimoto algorithm where the input is a stimulus vector composed of the time dependent concentrations of three PDT related cell death signaling molecules and a cell fate decision as output. The molecular concentrations are determined by a group of rate equations. The output is the cell decision with a probability of cell survival or death. The optimality of the cell decision strategy is assessed by the cell survival probability, which might be modified to account for heterogeneous cell resistance to therapy.