Toward a quantitative analysis of virus and plasmid trafficking in cells

TL;DR

This paper introduces a theoretical model for analyzing the microscopic trafficking of viruses and DNA in cells, combining diffusion and active transport, to better understand gene delivery mechanisms.

Contribution

It presents a homogenized stochastic model that captures cellular transport dynamics and estimates nuclear delivery success, advancing microscopic analysis of intracellular trafficking.

Findings

Model accurately predicts viral trajectories

Estimates mean time for nuclear delivery

Quantifies success probability of gene delivery

Abstract

Intracellular transport of DNA carriers is a fundamental step of gene delivery. We present here a theoretical approach to study generically a single virus or DNA particle trafficking in a cell cytoplasm. Cellular trafficking has been studied experimentally mostly at the macroscopic level, but very little has been done so far at the microscopic level. We present here a physical model to account for certain aspects of cellular organization, starting with the observation that a viral particle trajectory consists of epochs of pure diffusion and epochs of active transport along microtubules. We define a general degradation rate to describe the limitations of the delivery of plasmid or viral particles to the nucleus imposed by various types of direct and indirect hydrolysis activity inside the cytoplasm. Following a homogenization procedure, which consists of replacing the switching dynamics by a single steady state stochastic description, not only can we study the spatio-temporal dynamics of moving objects in the cytosol, but also estimate the probability and the mean time to go from the cell membrane to a nuclear pore. Computational simulations confirm that our model can be used to analyze and interpret viral trajectories and estimate quantitatively the success of nuclear delivery.