Stuffing a virus with DNA: Dissecting viral genome packaging

  1. Mark C. Williams*
  1. Department of Physics and Center for Interdisciplinary Research on Complex Systems, Northeastern University, Boston, MA 02115

It is rare that a fully functional biological system presents a simple biophysical problem. The problem of viral DNA packaging comes tantalizingly close: What forces are required to stuff double-stranded DNA of fixed length into a container of fixed volume? Now that biophysicists have developed the capability to measure such forces, theoretical solutions to this problem can be directly tested, as shown in the article by Fuller et al. (1) in this issue of PNAS. Because the theories describing these experiments involve relatively simple thermodynamics, the experiments present an excellent model system to test our understanding of DNA biophysics. Surprisingly, the authors find that recent models to describe DNA packaging in bacteriophages do not quantitatively predict the results of experiments in which solution conditions are changed.

Over the past several years, new techniques have been developed to measure the pressure required to hold packaged DNA inside a bacteriophage capsid (2–4) and the forces required to achieve such packaging (1, 5). These two complementary experiments have yielded several theoretical attempts to describe the biophysical mechanisms governing the DNA packaging and ejection processes. Because the biophysical properties of double-stranded DNA under a variety of solution conditions have been studied for many years, it should be possible to make detailed quantitative predictions for DNA packaging as solution conditions are varied.

Fig. 1.

Measurements of DNA packaging forces. (a) Schematic diagram of the optical tweezers experiment by Fuller et al. (1), in which the rate of DNA packaging by bacteriophage φ29 is measured as a function of force for high and low filling fractions. (b) Disagreement between theory and experiment may be due to the inability of the DNA to achieve an equilibrium structure during initial packaging. (c) Theoretical calculations of the internal packaging force assume an idealized DNA configuration.


Theoretical treatments of …

*E-mail: mark{at}neu.edu

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