ABSTRACT
This paper develops a transient three-kinetic state model that simulates rerouting of a pulse of axonal cargos that were initially misdirected to a dendrite. The following three cargo populations are included in the model: (i) anterogradely running cargos, (ii) retrogradely running cargos, and (iii) free (diffusion-driven) cargos that are detached from microtubules. The dynamics of cargo concentrations in various kinetic states are studied. It is demonstrated that the profile of the total cargo concentration is comprised of two major components. The first component is a pulse composed of anterogradely running cargos and the second component is a tail behind this pulse that is composed of free (diffusion-driven) and retrogradely running cargos. The total number of misdirected axonal cargos in the dendrite is also computed. The dependence of this quantity on the amount of time that passed from the moment when the pulse entered the dendrite and on kinetic constants describing transition rates between various kinetic states of misdirected cargos is investigated.
Subject(s)
Axonal Transport , Axons/metabolism , Dendrites/metabolism , Intracellular Space/metabolism , Models, Biological , Animals , Computational Biology , Computer Simulation , Diffusion , Intracellular Space/chemistry , MammalsABSTRACT
Viral gene delivery in a spherical cell is investigated numerically. The model of intracellular trafficking of adenoviruses is based on molecular-motor-assisted transport equations suggested by Smith and Simmons. These equations are presented in spherical coordinates and extended by accounting for the random component of motion of viral particles bound to filaments. This random component is associated with the stochastic nature of molecular motors responsible for locomotion of viral particles bound to filaments. The equations are solved numerically to simulate viral transport between the cell membrane and cell nucleus during initial stages of viral infection.
