Fig. 4.
Features and predictions of the limited conversion model compared with the simplified heterodimer conversion model. The limited conversion model posits that in fully infected cultures, when the cell accumulates high concentrations of PrPSc, the subpopulation of the PrPSc that is infectious (capable of self-catalysis) reaches saturation levels (Top). This assumption alleviates some of the experimental inconsistencies associated with treating the processes of PrPSc conversion, PrPSc degradation, and cell division as first-order reactions. The model explains the ability of cells in culture to attain stable levels of PrPSc when fully infected (Middle). It also provides an explanation for the ability of cells to achieve different steady-state levels of PrPSc when dividing at different rates (Bottom). In the simulation shown, stationary cells that have achieved a steady-state level of PrPSc are induced to divide at a time indicated by the arrow. In such a scenario, the simplified heterodimer model predicts a complete clearance of PrPSc over time, whereas the limited conversion model predicts a new steady-state level dictated by Eq. 6. The heterodimer model predicts an unstable state when [PrPC] is assumed to remain constant (as has been experimentally shown here). When this constraint is removed, the model is able to predict a stable state.