Effects of General Incidence and Polymer Joining on Nucleated Polymerization in a Model of Prion Proliferation

Two processes are incorporated into a new model for transmissible prion diseases. These are general incidence for the lengthening process of infectious polymers attaching to and converting noninfectious monomers, and the joining of two polymers to form one longer polymer. The model gives rise to a system of three ordinary differential equations, which is shown to exhibit threshold behavior dependent on the value of the parameter combination giving the basic reproduction number R0. For R00 \u3e1, the system is locally asymptotic to a positive disease equilibrium. The effect of both general incidence and joining is to decrease the equilibrium value of infectious polymers and to increase the equilibrium value of normal monomers. Since the onset of disease symptoms appears to be related to the number of infectious polymers, both processes may significantly inhibit the course of the disease. With general incidence, the equilibrium distribution of polymer lengths is obtained and shows a sharp decrease in comparison to the distribution resulting from mass action incidence. Qualitative global results on the disease free and disease equilibria are proved analytically. Numerical simulations using parameter values from experiments on mice (reported in the literature) provide quantitative demonstration of the effects of these two processes

Global stability for the prion equation with general incidence

We consider the so-called prion equation with the general incidence term introduced in [Greer et al., 2007], and we investigate the stability of the steady states. The method is based on the reduction technique introduced in [Gabriel, 2012]. The argument combines a recent spectral gap result for the growth-fragmentation equation in weighted $L^1$ spaces and the analysis of a nonlinear system of three ordinary differential equations

High-order WENO scheme for Polymerization-type equations

Polymerization of proteins is a biochimical process involved in different diseases. Mathematically, it is generally modeled by aggregation-fragmentation-type equations. In this paper we consider a general polymerization model and propose a high-order numerical scheme to investigate the behavior of the solution. An important property of the equation is the mass conservation. The fifth-order WENO scheme is built to preserve the total mass of proteins along time

Fragmentation and monomer lengthening of rod-like polymers, a relevant model for prion proliferation

The Greer, Pujo-Menjouet andWebb model [Greer et al., J. Theoret. Biol., 242 (2006), 598-606] for prion dynamics was found to be in good agreement with experimental observations under no-flow conditions. The objective of this work is to generalize the problem to the framework of general polymerization-fragmentation under flow motion, motivated by the fact that laboratory work often involves prion dynamics under flow conditions in order to observe faster processes. Moreover, understanding and modelling the microstructure influence of macroscopically monitored non-Newtonian behaviour is crucial for sensor design, with the goal to provide practical information about ongoing molecular evolution. This paper's results can then be considered as one step in the mathematical understanding of such models, namely the proof of positivity and existence of solutions in suitable functional spaces. To that purpose, we introduce a new model based on the rigid-rod polymer theory to account for the polymer dynamics under flow conditions. As expected, when applied to the prion problem, in the absence of motion it reduces to that in Greer et al. (2006). At the heart of any polymer kinetical theory there is a configurational probability diffusion partial differential equation (PDE) of Fokker-Planck-Smoluchowski type. The main mathematical result of this paper is the proof of existence of positive solutions to the aforementioned PDE for a class of flows of practical interest, taking into account the flow induced splitting/lengthening of polymers in general, and prions in particular.Comment: Discrete and Continuous Dynamical Systems - Series B (2012) XX-X