Chalmers Conferences, 9th European Conference on Mathematical and Theoretical Biology

Enzyme-Limited Nucleated Polymerization Model of Prion Aggregation
Jason Karl Davis, Suzanne S. Sindi

Last modified: 2014-06-09


Prions are associated with a number of fatal diseases in mammals and heritable phenotypes in yeast. Prions propagate through pathway that involves protein misfolding and aggregation. The mis-folded state is propagated through interactions between misfolded aggregates and normally folded protein monomers. Prion aggregates can also be fragmented into smaller complexes increasing the total number of aggregates converting the normal protein.


The dynamics of prion aggregation have been investigated mathematically through the analysis of aggregation-fragmentation ordinary or partial differential equations. However, most models assume the only molecular components are the prion and normal forms of the protein. For yeast prions, it has been shown that several molecular chaperones, such as Hsp104, are necessary for aggregate fragmentation. Since such chaperones are typically at low molecular concentrations, they act in a rate-limiting fashion. We extend the existing models of prion aggregate dynamics to include these chaperone dynamics, derive disease stability criteria for various parameter regimes, and interpret the original model's solution as the first term in a perturbation expansion of the solution to our equations.