Erik Werner

Confined polymers in the extended de Gennes regime

We show that the problem of describing the conformations of a semiflexible polymer confined to a channel can be mapped onto an exactly solvable model in the so-called extended de Gennes regime. This regime (where the polymer is neither weakly nor strongly confined) has recently been intensively studied experimentally and by means of computer simulations. The exact solution predicts precisely how the conformational fluctuations depend upon the channel width and upon the microscopic parameters characterizing the physical properties of the polymer.

Nanoconfined Circular and Linear DNA: Equilibrium Conformations and Unfolding Kinetics

Studies of circular DNA confined to nanofluidic channels are relevant both from a fundamental polymer-physics perspective and due to the importance of circular DNA molecules in vivo. We here observe the unfolding of confined DNA from the circular to linear configuration as a light-induced double-strand break occurs, characterize the dynamics, and compare the equilibrium conformational statistics of linear and circular configurations. This is important because it allows us to determine to what extent existing statistical theories describe the extension of confined circular DNA. We find that the ratio of the extensions of confined linear and circular DNA configurations increases as the buffer concentration decreases. The experimental results fall between theoretical predictions for the extended de Gennes regime at weaker confinement and the Odijk regime at stronger confinement. We show that it is possible to directly distinguish between circular and linear DNA molecules by measuring the emission intensity from the DNA. Finally, we determine the rate of unfolding and show that this rate is larger for more confined DNA, possibly reflecting the corresponding larger difference in entropy between the circular and linear configurations.

Monomer Distributions and Intrachain Collisions of a Polymer Confined to a Channel

We study the conformations of a self-avoiding polymer confined to a channel by computing the cross-sectional distributions of the positions of its monomers. By means of Monte Carlo simulations for a self-avoiding, freely jointed chain, we determine how the cross-sectional distribution for a given monomer depends on its location in the polymer and how strongly this distribution is affected by self-avoidance. To this end we analyze how the frequency of intrachain collisions between monomers depends on their spatial position in the channel and on their location within the polymer. We show that most collisions occur between closely neighboring monomers. As a consequence, the collision probability depends only weakly on the spatial position of the monomers. Our results explain why the effect of self-avoidance on the monomer distributions is weaker than predicted by mean-field theory. We discuss the relevance of our results for studies of DNA conformations in nanofluidic channels.

Orientational correlations in confined DNA

We study how the orientational correlations of DNA confined to nanochannels depend on the channel diameter D by means of Monte Carlo simulations and a mean-field theory. This theory describes DNA conformations in the experimentally relevant regime where the Flory-de Gennes theory does not apply. We show how local correlations determine the dependence of the end-to-end distance of the DNA molecule upon D. Tapered nanochannels provide the necessary resolution in D to study experimentally how the extension of confined DNA molecules depends upon D. Our experimental and theoretical results are in qualitative agreement.

Scaling regimes of a semiflexible polymer in a rectangular channel.

We derive scaling relations for the extension statistics and the confinement free energy for a semiflexible polymer confined to a channel with a rectangular cross section. Our motivation is recent numerical results [Gupta et al., J. Chem. Phys. 140, 214901 (2014)] indicating that extensional fluctuations are quite different in rectangular channels compared to square channels. Our results are of direct relevance for interpreting current experiments on DNA molecules confined to nanochannels, as many experiments are performed for rectangular channels with large aspect ratios, while theoretical and simulation results are usually obtained for square channels.

Finite-size corrections for confined polymers in the extended de Gennes regime.

Theoretical results for the extension of a polymer confined to a channel are usually derived in the limit of infinite contour length. But experimental studies and simulations of DNA molecules confined to nanochannels are not necessarily in this asymptotic limit. We calculate the statistics of the span and the end-to-end distance of a semiflexible polymer of finite length in the extended de Gennes regime, exploiting the fact that the problem can be mapped to a one-dimensional weakly self-avoiding random walk. The results thus obtained compare favorably with pruned-enriched Rosenbluth method (PERM) simulations of a three-dimensional discrete wormlike chain model of DNA confined in a nanochannel. We discuss the implications for experimental studies of linear λ-DNA confined to nanochannels at the high ionic strengths used in many experiments.

One-Parameter Scaling Theory for DNA Extension in a Nanochannel

Experiments measuring DNA extension in nanochannels are at odds with even the most basic predictions of current scaling arguments for the conformations of confined semiflexible polymers such as DNA. We show that a theory based on a weakly self-avoiding, one-dimensional “telegraph” process collapses experimental data and simulation results onto a single master curve throughout the experimentally relevant region of parameter space and explains the mechanisms at play.

Hairpins in the conformations of a confined polymer

If a semiflexible polymer confined to a narrow channel bends around by 180°, the polymer is said to exhibit a hairpin. The equilibrium extension statistics of the confined polymer are well understood when hairpins are vanishingly rare or when they are plentiful. Here, we analyze the extension statistics in the intermediate situation via experiments with DNA coated by the protein RecA, which enhances the stiffness of the DNA molecule by approximately one order of magnitude. We find that the extension distribution is highly non-Gaussian, in good agreement with Monte-Carlo simulations of confined discrete wormlike chains. We develop a simple model that qualitatively explains the form of the extension distribution. The model shows that the tail of the distribution at short extensions is determined by conformations with one hairpin.

Distribution of label spacings for genome mapping in nanochannels

In genome mapping experiments, long DNA molecules are stretched by confining them to very narrow channels, so that the locations of sequence-specific fluorescent labels along the channel axis provide large-scale genomic information. It is difficult, however, to make the channels narrow enough so that the DNA molecule is fully stretched. In practice, its conformations may form hairpins that change the spacings between internal segments of the DNA molecule, and thus the label locations along the channel axis. Here, we describe a theory for the distribution of label spacings that explains the heavy tails observed in distributions of label spacings in genome mapping experiments.