Ard Louis

Abstract:

By using oxDNA, a coarse-grained nucleotide-level model of DNA, we are able to directly simulate the self-assembly of a small 384-base-pair origami from single-stranded scaffold and staple strands in solution. In general, we see attachment of new staple strands occurring in parallel, but with cooperativity evident for the binding of the second domain of a staple if the adjacent junction is already partially formed. For a system with exactly one copy of each staple strand, we observe a complete assembly pathway in an intermediate temperature window; at low temperatures successful assembly is prevented by misbonding while at higher temperature the free-energy barriers to assembly become too large for assembly on our simulation time scales. For high-concentration systems involving a large staple strand excess, we never see complete assembly because there are invariably instances where two copies of the same staple both bind to the scaffold, creating a kinetic trap that prevents the complete binding of either staple. This mutual staple blocking could also lead to aggregates of partially formed origamis in real systems, and helps to rationalize certain successful origami design strategies.

Abstract:

The rupture of double-stranded DNA under stress is a key process in biophysics and nanotechnology. In this article, we consider the shear-induced rupture of short DNA duplexes, a system that has been given new importance by recently designed force sensors and nanotechnological devices. We argue that rupture must be understood as an activated process, where the duplex state is metastable and the strands will separate in a finite time that depends on the duplex length and the force applied. Thus, the critical shearing force required to rupture a duplex depends strongly on the time scale of observation. We use simple models of DNA to show that this approach naturally captures the observed dependence of the force required to rupture a duplex within a given time on duplex length. In particular, this critical force is zero for the shortest duplexes, before rising sharply and then plateauing in the long length limit. The prevailing approach, based on identifying when the presence of each additional base pair within the duplex is thermodynamically unfavorable rather than allowing for metastability, does not predict a time-scale-dependent critical force and does not naturally incorporate a critical force of zero for the shortest duplexes. We demonstrate that our findings have important consequences for the behavior of a new force-sensing nanodevice, which operates in a mixed mode that interpolates between shearing and unzipping. At a fixed time scale and duplex length, the critical force exhibits a sigmoidal dependence on the fraction of the duplex that is subject to shearing.