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What are the Physical Properties - Branching Characteristics and 3D sizes - of viral-length RNA molecules?

The figure to the left is a cryo-electron microscopy image that we obtained [RNA 2012] from a purified solution of the RNA molecules (circled in red) corresponding to one of the genes of CCMV. Each of the molecules in the micrograph is chemically identical to the others – the same 3200 nucleotide (nt)-long sequence of RNA. But they appear different because they have different secondary and tertiary structures and because they have different orientations in the vitreous water in which they are trapped at low temperature; accordingly, they have different 2D projections in the transmission micrograph. Indeed, an RNA molecule this long must be regarded as a “statistical object” that must be represented by an ensemble of configurations, much like a long semi-flexible polymer.



Virus particles can be as simple as a molecule of RNA or DNA inside a spherical shell – the “capsid” – made up of multiple copies of a single protein. Further, because viruses only “become alive” when they are inside their hosts, it is possible to study them as physical objects, i.e., to do the same controlled experiments (and theory) on them that one routinely does with more familiar polymer and colloidal systems.

Our Groups' Previous Work in Studying the Pressure of DNA Viruses - Packing DNA in Bacteriophage

Bacteriophage lambda, shown in the electron micrograph, consists of a protein capsid 30 nm in radius that has a long cylindrical tail. Its genome, double stranded DNA (dsDNA), is protected by the capsid from attack by nuclease enzymes that would break it down into its nucleotides and therefore lose the genetic information needed to replicate the phage. The DNA contains 48.6 kilo-base pairs; if it were fully extended it would be 17 micrometers long. When the phage is replicated in the host cell, an early form of the capsid, the procapsid, is formed and the DNA is driven into it by a molecular motor at one of the procapsid vertices. This is quite feat! Imagine packing a length of string into an object that is only 1/400th its size. To make the job harder, add negative charges to the string and make it stiff. The stiffness of ds DNA is very high; a measure of this stiffness is its persistence length. It is difficult to bend objects on a scale smaller than the persistence length. The persistence length of dsDNA is 50 nm, and to bend it so that it can fit into the capsid is therefore highly costly in energy.

The Origin of Icosahedral Symmetry in Viruses

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Certainly one of the most intriguing facts about viruses is that the large majority of them display full icosahedral symmetry, arguably the highest and also the most esthetically-pleasing symmetry shown in Nature. The elements of icosahedral symmetry involve 6 five-fold rotation axes, 10 three-fold, and 15 two-fold. The figure to the right shows a number of examples, including the 60nm-diameter human papilloma virus at one end and 28nm CCMV near the other; similar image reconstructions for still larger viruses, up to the 100nm-diameter herpes simplex virus, are available from cryo-EM and X-ray work (Figure from Review by Baker et al.).
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