The persistence length and length per base of single-stranded DNA obtained from fluorescence correlation spectroscopy measurements using mean field theory

Chi, Qingjia; Wang, Guixue; Jiang, Jiahuan

doi:10.1016/j.physa.2012.09.022

Cited by 126 publications

(131 citation statements)

References 44 publications

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“…Dynamic light scattering confirmed that conjugates with longer DNA bridges were more extended (Figure 2A), supporting the use of dsDNA as a ruler. Inter-Fab distances calculated from dsDNA lengths were regarded as approximate because the DNA linkers included short regions of ssDNA (persistence length 22 Å) (Chi et al, 2013) to permit orientational flexibility.…”

Section: Resultsmentioning

confidence: 99%

Intra-Spike Crosslinking Overcomes Antibody Evasion by HIV-1

Galimidi

Klein

Politzer

et al. 2015

Cell

114

136

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SUMMARY Antibodies developed during HIV-1 infection lose efficacy as the viral spike mutates. We postulated that anti-HIV-1 antibodies primarily bind monovalently because HIV’s low spike density impedes bivalent binding through inter-spike crosslinking, and the spike structure prohibits bivalent binding through intra-spike crosslinking. Monovalent binding reduces avidity and potency, thus expanding the range of mutations permitting antibody evasion. To test this idea, we engineered antibody-based molecules capable of bivalent binding through intra-spike crosslinking. We used DNA as a “molecular ruler” to measure intra-epitope distances on virion-bound spikes and construct intra-spike crosslinking molecules. Optimal bivalent reagents exhibited up to 2.5 orders-of-magnitude increased potency (>100-fold average increases across virus panels) and identified conformational states of virion-bound spikes. The demonstration that intra-spike crosslinking lowers the concentration of antibodies required for neutralization supports the hypothesis that low spike densities facilitate antibody evasion and the use of molecules capable of intra-spike crosslinking for therapy or passive protection.

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Section: Resultsmentioning

confidence: 99%

Intra-Spike Crosslinking Overcomes Antibody Evasion by HIV-1

Galimidi

Klein

Politzer

et al. 2015

Cell

114

136

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“…In addition, the persistence length for ssDNA molecules is around 2–4 nm which, owing to a larger degree of freedom, is significantly smaller than that for dsDNA (50 nm) molecules. [63,64] The stiffer dsDNA molecule has weak interactions with the membrane surface and could be expected to be linearly oriented (Figure 6A) under the influence of the strong local electric field and translocate much faster than the ssDNA molecules. On the other hand, a ssDNA molecule can easily orient along the graphene surface and enter the nanopore through a 2D diffusion process which would significantly slow down DNA translocations as confirmed by our results.…”

Section: Resultsmentioning

confidence: 99%

Slowing DNA Transport Using Graphene–DNA Interactions

Banerjee

Wilson

Shim

et al. 2014

Adv Funct Materials

111

106

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Slowing down DNA translocation speed in a nanopore is essential to ensuring reliable resolution of individual bases. Thin membrane materials enhance spatial resolution but simultaneously reduce the temporal resolution as the molecules translocate far too quickly. In this study, the effect of exposed graphene layers on the transport dynamics of both single (ssDNA) and double-stranded DNA (dsDNA) through nanopores is examined. Nanopore devices with various combinations of graphene and Al2O3 dielectric layers in stacked membrane structures are fabricated. Slow translocations of ssDNA in nanopores drilled in membranes with layers of graphene are reported. The increased hydrophobic interactions between the ssDNA and the graphene layers could explain this phenomenon. Further confirmation of the hydrophobic origins of these interactions is obtained through reporting significantly faster translocations of dsDNA through these graphene layered membranes. Molecular dynamics simulations confirm the preferential interactions of DNA with the graphene layers as compared to the dielectric layer verifying the experimental findings. Based on our findings, we propose that the integration of multiple stacked graphene layers could slow down DNA enough to enable the identification of nucleobases.

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“…In order to obtain information about the sequence of a genome, the DNA molecule must be unzipped to form ssDNA, which possess different properties than dsDNA. Importantly, the persistent length of ssDNA is ~2 nm [107] which is roughly 25 times less than that of dsDNA. This is potentially troublesome, as herniation or hooking would be able to occur in much more compact gels, which could lead to nanopore clogging, similar to the case of the agarose-interfaced nanopore with large DNA fragments.…”

Section: Discussionmentioning

confidence: 99%

Interfacing solid‐state nanopores with gel media to slow DNA translocations

et al. 2015

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We demonstrate the ability to slow DNA translocations through solid‐state nanopores by interfacing the trans side of the membrane with gel media. In this work, we focus on two reptation regimes: when the DNA molecule is flexible on the length scale of a gel pore, and when the DNA behaves as persistent segments in tight gel pores. The first regime is investigated using agarose gels, which produce a very wide distribution of translocation times for 5 kbp dsDNA fragments, spanning over three orders of magnitude. The second regime is attained with polyacrylamide gels, which can maintain a tight spread and produce a shift in the distribution of the translocation times by an order of magnitude for 100 bp dsDNA fragments, if intermolecular crowding on the trans side is avoided. While previous approaches have proven successful at slowing DNA passage, they have generally been detrimental to the S/N, capture rate, or experimental simplicity. These results establish that by controlling the regime of DNA movement exiting a nanopore interfaced with a gel medium, it is possible to address the issue of rapid biomolecule translocations through nanopores—presently one of the largest hurdles facing nanopore‐based analysis—without affecting the signal quality or capture efficiency.

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The persistence length and length per base of single-stranded DNA obtained from fluorescence correlation spectroscopy measurements using mean field theory

Cited by 126 publications

References 44 publications

Intra-Spike Crosslinking Overcomes Antibody Evasion by HIV-1

Intra-Spike Crosslinking Overcomes Antibody Evasion by HIV-1

Slowing DNA Transport Using Graphene–DNA Interactions

Interfacing solid‐state nanopores with gel media to slow DNA translocations

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