Force responses of strongly intrinsically curved DNA helices deviate from worm-like chain predictions

Abstract

DNA sequences with nontrivial intrinsic curvature are of interest for a range of biological and artificial DNA systems. We design both intrinsically strongly curved and intrinsically straight sequences. We find that such sequences with opposing curvatures can be designed even under constraints that would naively lead one to assume that those sequences would be highly similar in their mechanical properties. We then characterize the force response of those sequences and find that their force-extension curves deviate significantly in the low-force regime, and that the standard worm-like chain description is inadequate to describe the low-force response of the strongly bent sequences. We propose a modified description that takes the intrinsic curvature into account, making the DNA act, in the low-force regime, like a nanoscale helical spring. We find strongly improved agreement between the model and the simulated force-extension curves.

Deciphering the mechanical properties of B‐DNA duplex

“…225 The standard WLC description is inadequate for molecules with macroscopic curvature, such as phased A-tracts. 164,226 The problem is the static shape, whereas the thermally induced fluctuations may still resemble those of a straight molecule. It is therefore desirable to separate the static part from the thermal noise.…”

Tensile elasticity of semiflexible polymers with hinge defects

“…Some important biopolymers, however, exhibit behavior which cannot be accounted for by the simple uniform and isotropic WLC model. One example is the spontaneous curvature in tubulin protofilaments, in bacterial FtsZ or in some cases of eukareotic DNA [4][5][6]. In addition, starting with the pioneering experimental work of Cloutier and Widom, it has become clear that short ds-DNA molecules [7] exhibit highly bendable behavior on short length scales [8,9].…”

Performing SELEX experiments in silico

“…The top panel shows the results using the Rosanio sequence; the bottom uses the artificially designed, very strongly intrinsically bent sequence from Ref. 34. The fixed sequences significantly bias the ring to a subrange of rotational states; the artificially designed sequence biases far more strongly than does the Rosanio sequence, for which reason we will employ it later on.…”

“…All rings are direction-biased not using the locking sequence of Rosanio et al, but with the artificial, strongly bent sequence from Ref. 34, described in Sec. V. We chose this sequence over the locking sequence from Rosanio et al because of the stronger and cleaner directional bias (see Fig.…”

“…The total frequency of the A/T-rich dinucleotides (AA/AT/TA/TT) for three different rings, all directionally biased using the artificial locking sequence from Ref 34. (see Sec.…”