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Biophys. J. BioFAST: First Published June 24, 2005. doi:10.1529/biophysj.105.059477
© 2005 by the Biophysical Society.

A more recent version of this article appeared on September 1, 2005.
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BIOPHYSICAL THEORY AND MODELING

A Model for Intracellular Trafficking of an Adenovirus

Anh-Tuan Dinh 1, Thro Theofanous 1 and Samir Mitragotri 2*

1 University of California, Santa Barbara
2 University Of California, Santa Barbara

* To whom correspondence should be addressed. E-mail: samir{at}engineering.ucsb.edu.

Submitted on January 11, 2005
Revised on April 13, 2005
Accepted on 13 June 2005


  Abstract
Here we develop an integrative computational framework to model biophysical processes involved in viral gene delivery. The model uses reaction-diffusion-advection equations that describe intracellular trafficking in combination with kinetic equations that describe transcription and translation of the exogenous DNA. It relates molecular-level microtubular binding and trafficking events to whole-cell distribution of viruses. The approach makes use of current understanding of cellular processes and data from single-particle single-cell imaging experiments. The model reveals two important parameters that characterize viral transport at the population level, namely, the effective velocity, Veff and the effective diffusion coefficient Deff. Veff measures virus's net movement rate and Deff represents the total dispersion rate. We employ the model to study the influence of microtubule-mediated movements on nuclear targeting and gene expression of adenoviruses in HeLa and A549 cells. Effects of microtubule organization and dynamics and the presence of microtubule-destabilizing drug were analyzed and quantified. Model predictions agree well with experimental data available in literature. The paper serves as a guide for future theoretical and experimental efforts to understand viral gene delivery.

Key Words: Adenovirus, Intracellular Transport,, Microtubule, Motor-Assisted Transport,, Simulation, Viral Gene Delivery




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Copyright © 2005 by the Biophysical Society.