Figure 5.

Use of scaling analysis to determine the mechanism of replication in a living system. The concentration of prions was determined as a function of time after inoculation by prions in a number of different mouse lines, with technical and biological replicates shown as solid points (A–D). The mouse lines express the different amounts of the monomeric precursor, PrP, as shown in (E) relative to the wild type line Prnp^+/+. The rate of replication is extracted from those data by fitting of a minimal model (solid lines). In turn, the variation of the replication rate with the concentration of the precursor protein PrP allows one to determine the scaling exponent, γ = 0.6 (E). This low scaling, with the rate increasing approximately with the square root of the protein concentration, allows a range of mechanisms to be excluded and is consistent with the mechanism of prion multiplication determined for the purified protein in vitro. Adapted from Meisl et al. (2021b).