Specific lysis modeling and parameter extraction from experimental data

Specific lysis is a complex multi-step process of target cell death mediated by cytotoxic granules containing enzymes (perforins, granzymes) that are released by effector cells after engagement with a target. It is also known that the probability of target lysis should depend on the number of surrounding effector cells (i.e., effector to target ratio). Since the cell-cell interactions during target killing are discrete processes and an exact number of certain cell aggregates is unknown, a detailed description of cell lysis is complicated and contains plenty of parameters. This work aims to provide simple biologically relevant equations describing cell lysis dependence on both time and effector-target ratio. The derived equations were validated against different types of experimental data on T and NK cell cytotoxic activity and exhibited saturation behavior at increasing concentration of both effector and target cells according to observations. Thereby, our approach allows calculating the parameters of cell lysis (rate constant and EC50 values) from experimental data without a curve fitting.