Pathway Complexity of the Self-Assembly of Linear Viruses and Virus-Like Particles

Abstract

The capsid of linear virus-like particles and viruses are created by a self-assembly process in a solution containing the coat proteins and genome. The self-assembly may take place via different, molecular pathways, which are influenced by the associated binding free energies. Measurements of the self-assembly of virus-like particles show an overshoot in the capsid assembly and an increase of the total protein density may result in a smaller percentage of fully encapsulated particles. These observations are possibly due to the assembly of micelles in the solution. In this thesis a model, which is a combination of three known models, is proposed for describing the assembly-pathways. This model considers a cooperative and non-cooperative capsid assembly, the assembly of micelles in the solution, and a nucleation barrier. The equilibrium properties and dynamics of this model show a high dependence on the relation between the critical density of each binding mode, the overall density of the proteins and the stoichiometry. The occurrence of an overshoot in the capsid assembly seen experimentally follows from a slow micelle assembly. However, according to this model, an increase of the total protein concentration can not result in a lower probability of a fully encapsulated particle.