Hey hey hey hey, it was the DNA

In 1977, years before the human genome project [1] and a spate of poorly considered media reports of specific genes for this, that and the other, the British rock band Queen had already declared on their News of the World album that 'it was the DNA, that made me feel that way'. Few other biological macromolecules have obtained the iconic status of DNA, the 'blueprint of life'. While understanding its capacity for the storage and the transmission of information and how it is exploited in the biological context of the cell is surely fascinating, it has been largely its physical properties that have caught the attention of physicists.

In particular, the tools of molecular biology can now routinely be exploited to produce ensembles of DNA molecules that all possess the same sequence, and hence length. Indeed the fact that every laboratory around the world potentially has the technology to produce physically identical polymeric molecules has promoted DNA to the status of a molecular standard in metrology experiments, for example in single molecule force spectroscopy [2, 3].

In addition to the facile production of polymer chains with controlled lengths, a feat that still eludes the best efforts of synthetic chemistry, the ability to use polymerase chain reaction (PCR) to place the four DNA bases in controllable sequences on demand, coupled with the ability to successfully predict which bases hydrogen bond with which, has led to the field of DNA bionanotechnology [4]. Here the pairing rules are used to design polymers that are pre-programmed to assemble, either into complex intramolecular sculptures, epitomised by the smiling faces of DNA origami [5], or multi-polymer hierarchical structures [6]. How such sequences are manifest in the cell in order to create, for example, local quadruplex structures, that can impede molecular machines and thereby turn off processes of transcription are of primary interest to scientists attempting to understand both aging and cancer [7, 8].

In a recent paper Glaser et al (2016 New J. Phys. 18 055001) have exploited this programmable assembly to produce DNA nanotubes [9] consisting of different numbers of individual DNA molecules (between 4 and 10). Crucially, while the diameter of these tubes do not vary significantly, the persistence lengths vary by an order of magnitude [10]. The persistence length, the decay constant characterising the loss of correlation of the directions of tangent vectors to the chain backbone as its length is traversed, represents the competition between the bending modulus of the chain and thermal flucuations, and as such can be regarded as a mechanical measurment. This gives the system investigated a rather unique possibility, to isolate the effects of the mechanical properties of the nanotubes on the largescale behaviours of the system, without changing the chemical nature of the tubes.

Encouraging the nanotubes in the solution to interact via depletion potentials induced by the presence of a relatively small polymer (PEG), or by exploiting oligomeric DNA staples, results in the emergence of patterning at larger length scales. This kind of mesoscopic organisation is signposted in the classic work of Onsager [11], and given the important role of the competition between translational and rotational entropy, being able to isolate the effect the mechanical properties of the nanotubes makes the system elaborated by Glaser et al an ideal model for investigation.

Their studies elegantly confirm that, from an initially isotropic state, the assembly of the nanotubes into a variety of different structures at larger lengthscales does not require specific interactions to be designed, and indeed is a general feature of the physics of introducing non-specific attractive interactions. Proposed state diagrams are used to demarcate areas of different emergent structures as a function of the DNA concentration and the PEG content, and it is clear that changing the mechanical properties of the tubes does indeed modify the behaviour, presumably playing out by redistributing the entropy within the systems. The most flexible tubes primarily give rise to isolated star or aster-like bundles or their networks, while those with longer persistence lengths can uniquely exhibit ordered needle-like structures. At high interaction strengths and DNA concentrations condensed aggregates result. Using these systems to investigate how the architecture of these hierarchically assembled networks modifies the resultant stress-bearing pathways and rheological behaviour would also seem a ripe area for investigation.

Interestingly, exploiting more specific inter-tube interactions, by designing small DNA fragments that could staple together pre-formed tubes, similar density fluctuations to those generated with the non-specific depletion interactions could be reproduced. However, these systems showed significantly more evidence of the kinetic trapping of structures, presumably owing to a combination of increased rates of formation and slower internal dynamics. Whether functional biopolymeric structures in Nature are predominantly controllably trapped appears unclear, but certainly this would offer more responsiveness and flexibility than a system closer to its global free energy minimum. These studies also provide insight into the effects of increasing the density of the components on the larger lengthscale assemblies realised. This has considerable bearing on the understanding of molecular crowding [12] and promises to address fundamental questions about the effects of the presence of the myriad of other components found in the cell's interior on the structure and dynamics of biopolymeric assemblies.

In Queen's song Shear Heart Attack, DNA spawned the inarticulate. But as the tools of molecular biology and biophysics continue to advance it is clear that studying the living world can offer verbose and elequent instantiations of the laws of physics.