Skip to main content
Log in

Modeling DNA and Virus Trafficking in the Cell Cytoplasm

  • Published:
Journal of Statistical Physics Aims and scope Submit manuscript

Abstract

Cytosol trafficking is a limiting step of viral infection or DNA delivery. Starting from the cell surface, most viruses have to travel through a crowded and risky environment in order to reach a small nuclear pore. This work is dedicated to estimating the probability p N of a viral arrival success and, in that case, the mean time τ N it takes. Viral movement is described by a stochastic equation, containing both a drift and a Brownian component. The drift part represents the movement along microtubules, while the Brownian component corresponds to the free diffusion. The success of a viral infection is limited by a killing activity occurring inside the cytoplasm. We model the killing activity by a steady state killing rate k. Because nuclear pores occupy a small fraction of the nuclear area, we use this property to obtain asymptotic estimates of p N and τ N as a function of the diffusion constant D, the amplitude of the drift B and the killing rate k.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. E. Dauty and A. S. Verkman, Actin cytoskeleton as the principal determinant of size-dependent DNA mobility in cytoplasm: a new barrier for non-viral gene delivery. J. Biol. Chem. 280(9):7823–7828 (2005).

    Article  Google Scholar 

  2. P. G. De Gennes, Scaling Concepts in Polymer Physics (Cornell University Press, Ithaca, NY, 1979).

    Google Scholar 

  3. A. T. Dinh, T. Theofanous, and S. Mitragotri, A model for intracellular trafficking of adenoviral vectors. Biophys. J. 89(3):1574–1588 (2005).

    Article  Google Scholar 

  4. W. Ding, L. Zhang, Z. Yan, and J. F. Engelhardt, Intracellular trafficking of adeno-associated viral vectors. Gene Ther. 12:873–880 (2005).

    Article  Google Scholar 

  5. K. Dohner, C. H. Nagel, and B. Sodeik, Viral stop-and-go along microtubules: taking a ride with dynein and kinesins. Trends Microbiol. 13(7):320–327 (2005).

    Article  Google Scholar 

  6. P. R. Garabedian, Partial Differential Equations (John Wiley Sons, Inc., New York-London-Sydney, 1964).

    MATH  Google Scholar 

  7. U. F. Greber and M. Way, A superhighway to virus infection. Cell 124(4):741–754 (2006).

    Article  Google Scholar 

  8. N. Hirokawa, Kinesin and dynein superfamily proteins and the mechanism of organelle transport. Science 279(5350):519–526 (1998).

    Article  ADS  Google Scholar 

  9. D. Holcman, A. Marchevska, and Z. Schuss, The survival probability of diffusion with trapping in cellular biology. Phys. Rev. E Stat, Nonlin. Soft. Matter Phys. 72:031910 (2005).

    ADS  Google Scholar 

  10. D. Holcman and Z. Schuss, Escape through a small opening: receptor trafficking in a synaptic membrane. J. Stat. Phys. 117(5–6):975–1014 (2004).

    Article  MATH  MathSciNet  Google Scholar 

  11. T. Lagache and D. Holcman, Effective drift of a virus trafficking inside a biological cell, pre-print.

  12. D. Lechardeur, Metabolic instability of plasmid DNA in the cytosol: a potential barrier to gene transfer. Gene Ther. 6:482–497 (1999).

    Article  Google Scholar 

  13. G. G. Maul and L. Deaven, Quantitative determination of nuclear pore complexes in cycling cells with differing DNA content. J. Cell. Biol. 73(3):748–760 (1977)

    Article  Google Scholar 

  14. P. Palese, Influenza: Old and new threats. Nat Med. 10(12 Suppl):S82-87 (2004).

    Article  Google Scholar 

  15. J. F. Cros and P. Palese, Trafficking of viral genomic RNA into and out of the nucleus: influenza, Thogoto and Borna disease viruses. Virus Res. 95(1–2):3–12 (2003).

    Article  Google Scholar 

  16. Z. Schuss, Theory and Applications of Stochastic Differential Equations, Wiley Series in Probability and Statistics (John Wiley & Sons, Inc., New York, 1980).

    Google Scholar 

  17. G. Seisenberger, M. U. Ried, T. Endress, H. Buning, M. Hallek, and C. Brauchle, Real-time single-molecule imaging of the infection pathway of an adeno-associated virus. Science 294(5548):1929–1932 (2001).

    Article  ADS  Google Scholar 

  18. A. Singer, Z. Schuss, D. Holcman, and R. S. Eisenberg, Narrow escape. I. J. Stat. Phys. 122(3):437–463 (2006).

    Article  MATH  MathSciNet  Google Scholar 

  19. A. Singer, Z. Schuss, and D. Holcman, Narrow escape. II. The circular disk. J. Stat. Phys. 122(3):465–489 (2006).

    Article  MATH  MathSciNet  Google Scholar 

  20. A. Singer, Z. Schuss, and D. Holcman, Narrow escape. III. Non-smooth domains and Riemann surfaces. J. Stat. Phys. 122(3):491–509 (2006).

    Article  MATH  MathSciNet  Google Scholar 

  21. A. Singer and Z. Schuss, Activation through a narrow opening. Phys. Rev. E Stat. Nonlin. Soft. Matter Phys. 74:020103 (2006).

    Google Scholar 

  22. G. A. Smith and L. W. Enquist, Break ins and break outs: viral interactions with the cytoskeleton of Mammalian cells. Annu. Rev. Cell. Dev. Biol. 18:135–161 (2002).

    Article  Google Scholar 

  23. M. Suomalainen, M. Y. Nakano, S. Keller, K. Boucke, R. P. Stidwill, and U. F. Greber, Microtubule-dependent plus- and minus end-directed motilities are competing processes for nuclear targeting of adenovirus. J. Cell Biol. 144(4):657–672 (1999).

    Article  Google Scholar 

  24. G. Zuber, E. Dauty, M. Nothisen, P. Belguise, and J. P. Behr, Towards synthetic viruses. Adv. Drug Deliv. Rev. 52:245–253 (2001).

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to D. Holcman.

Additional information

This paper is dedicated to my wife Nathalie Rouach.

D. H. is supported by the program “Chaire d’Excellence.”

D.H is incumbent to the Haas Russell Chair

Rights and permissions

Reprints and permissions

About this article

Cite this article

Holcman, D. Modeling DNA and Virus Trafficking in the Cell Cytoplasm. J Stat Phys 127, 471–494 (2007). https://doi.org/10.1007/s10955-007-9282-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10955-007-9282-4

Keywords

Navigation