Quantitative analysis of virus and plasmid trafficking in cells.
Intracellular transport of DNA carriers is a fundamental step of gene delivery. By combining both theoretical and numerical approaches we study here single and several viruses and DNA particles trafficking in the cell cytoplasm to a small nuclear pore. We present a physical model to account for certain aspects of cellular organization, starting with the observation that a viral 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 a nuclear pore imposed by various types of direct and indirect hydrolysis activity inside the cytoplasm. By replacing the switching dynamics by a single steady state stochastic description, we obtain estimates for the probability and the mean time for the first one of many particles to go from the cell membrane to a small 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.
Lagache
Thibault
T
Département de Mathématiques et de Biologie, Ecole Normale Supérieure, 46 rue d'Ulm 75005 Paris, France.
Dauty
Emmanuel
E
Holcman
David
D
D001692:Biological Transport; D002467:Cell Nucleus / Q000378:metabolism; D002477:Cells / Q000166:cytology / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D004058:Diffusion; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000378:metabolism; D006868:Hydrolysis; D008870:Microtubules / Q000378:metabolism; D008954:Models, Biological; D009068:Movement; D010957:Plasmids / Q000378:metabolism*; D016062:Porosity; D011336:Probability; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D013997:Time Factors; D014780:Viruses / Q000378:metabolism*
D004247:DNA; D046988:Proteasome Endopeptidase Complex