Speaker
Description
Prion fibril assemblies exhibit a strong structural and dynamical heterogeneity that cannot be described by classical linear polymerization models.
Using single-assembly imaging and bulk kinetic measurements, we show that fibrillar and oligomeric subpopulations coexist and continuously exchange material through catalytically mediated processes. At the population level, this exchange generates spontaneous depolymerization, damped oscillations, and multi-timescale relaxation dynamics, indicating that prion assemblies evolve far from equilibrium and form a non-linear dynamical system with multiple interacting species. These experimental observations provide quantitative constraints for a minimal kinetic framework based on catalytic feedback and exchange between subpopulations. Embedded in a reaction–diffusion setting, this framework was used to explore how non-linear replication dynamics shape prion spreading in tissue. The model reveals the emergence of attractor states, strain-dependent propagation regimes, and non-trivial strain interference and co-propagation, arising solely from kinetic non-linearities and feedback rather than tissue-specific templating. Overall, this work illustrates how experimentally grounded non-linear dynamics at the assembly level can control large-scale spreading and strain behavior.
