One-Parameter Scaling Theory for DNA Extension in a Nanochannel

Werner, Erik; Cheong, Guo Kang; Gupta, Damini; Dorfman, Kevin D.; Mehlig, B.

doi:10.1103/physrevlett.119.268102

Cited by 30 publications

(85 citation statements)

References 49 publications

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“…Werner et al developed a one-parameter theoretical prediction for estimating the physical properties of DNA for square nanochannels in this size range. [21] In the Supporting Information, we demonstrate how this prediction can be used to estimate the persistence length of DNA, with and without aS bound, by approximating the rectangular channel size by its geometric mean (Supporting Information data analysis, Figures S2 and S3). The conclusion from this analysis is that the persistence length gradually increases from around 70 nm for naked DNA to around 90 nm for DNA with 40 μm aS added (Figure 2).…”

Section: Resultsmentioning

confidence: 99%

Alpha‐Synuclein Modulates the Physical Properties of DNA

Jiang

Rocha

Westling

et al. 2018

Chemistry A European J

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Fundamental research on Parkinson’s disease (PD) most often focuses on the ability of α-synuclein (aS) to form oligomers and amyloids, and how such species promote brain cell death. However, there are indications that aS also plays a gene-regulatory role in the cell nucleus. Here, the interaction between monomeric aS and DNA in vitro has been investigated with single-molecule techniques. Using a nanofluidic channel system, it was discovered that aS binds to DNA and by studying the DNA–protein complexes at different confinements we determined that aS binding increases the persistence length of DNA from 70 to 90 nm at high coverage. By atomic force microscopy it was revealed that at low protein-to-DNA ratio, the aS binding occurs as small protein clusters scattered along the DNA; at high protein-to-DNA ratio, the DNA is fully covered by protein. As DNA-aS interactions may play roles in PD, it is of importance to characterize biophysical properties of such complexes in detail.

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Section: Resultsmentioning

confidence: 99%

Alpha‐Synuclein Modulates the Physical Properties of DNA

Jiang

Rocha

Westling

et al. 2018

Chemistry A European J

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“…Thus, if the DNA has contour length L and is in a linear (unfolded) state in the nanochannel, the extension X U is given as X U = α U L. In the extended de Gennes regime, the value of the prefactor α U is known exactly, [34] and for stronger confinement the values were computed in Ref. [40]. In the circular (folded) state, the molecule has extension X F = α F L 2 , see Fig.…”

Section: Summary and Discussionmentioning

confidence: 99%

“…[29,30,31,34] Since the channel width is of the order of the persistence length of the DNA molecule, our system is in fact in between these two regimes. However, it was recently shown that the underlying physics is the same in the different regimes, [40] only prefactors in the estimates of forces and mobilities may differ. In particular, the force f is independent of the extension, and the mobility is inversely proportional to the extension.…”

Section: B U L W U O O J K M C X 3 a C Z + D C J T T G B P R Q A G J mentioning

confidence: 99%

“…Stiffness, self avoidance, and confinement compete in determining the DNA extension, giving rise to a multitude of apparently distinct physical regimes. Recently it was shown, [40] however, that the problem of determining the steady-state extension distribution of nano-confined DNA can be mapped to a single stochastic, telegraph model that describes the DNA conformations as random yet persistent random walks. This theory predicts the universal scaling properties of the steady-state extension distribution over a wide range of parameters.…”

Section: Introductionmentioning

confidence: 99%

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Stochastic unfolding of nanoconfined DNA: Experiments, model and Bayesian analysis

Krog

Alizadehheidari

Werner

et al. 2018

The Journal of Chemical Physics

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Nanochannels provide means for detailed experiments on the effect of confinement on biomacromolecules, such as DNA. We here introduce a model for the complete unfolding of DNA from the circular to linear configuration. Two main ingredients are the entropic unfolding force as well as the friction coefficient for the unfolding process, and we describe the associated dynamics by a nonlinear Langevin equation. By analyzing experimental data where DNA molecules are photo-cut and unfolded inside a nanochannel, our model allows us to extract values for the unfolding force as well as the friction coefficient for the first time. In order to extract numerical values for these physical quantities, we employ a recently introduced Bayesian inference framework. We find that the determined unfolding force is in agreement with estimates from a simple Flory type argument. The estimated friction coefficient is in agreement with theoretical estimates for motion of a cylinder in a channel. We further validate the estimated friction constant by extracting this parameter from DNA's center-of-mass motion before and after unfolding, yielding decent agreement.

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“…To compute the distribution of label spacings along the channel axis, we use the model derived in Ref. 32, projecting the three-dimensional DNA configurations x(t) onto the channel axis x. The model consists of two parts: an ideal correlated random walk, and a bias that takes into account self avoidance.…”

Section: Telegraph Modelmentioning

confidence: 99%

Distribution of label spacings for genome mapping in nanochannels

et al. 2018

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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.

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One-Parameter Scaling Theory for DNA Extension in a Nanochannel

Cited by 30 publications

References 49 publications

Alpha‐Synuclein Modulates the Physical Properties of DNA

Alpha‐Synuclein Modulates the Physical Properties of DNA

Stochastic unfolding of nanoconfined DNA: Experiments, model and Bayesian analysis

Distribution of label spacings for genome mapping in nanochannels

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