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Browsing by Author "Bhandari, Aditya Bikram"

Now showing 1 - 6 of 6
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    Bridging the gap between theory, experiments and simulations of nanochannel confined DNA
    (2020-08) Bhandari, Aditya Bikram
    The study of nanochannel confined DNA has garnered substantial attention since the early 2000's owing to its application in genome mapping, the coarse-grained counterpart to DNA sequencing, which is an indispensable tool in biological research. However, our understanding of the physics behind confined DNA is rather simplified and incomplete. Thus, theory, simulation and experiment have by and large been at odds with one another. The results of this dissertation are aimed at understanding and attempting to resolve the source of these discrepancies. Our strategy for this dissertation is three-pronged. First, we revisit a historically cited explanation for the discrepancies - the lack of understanding behind the wall depletion length denoting the wall-DNA electrostatic interactions. Second, we considered the intersection of theory and simulation, which recent developments have managed to bring sufficiently into accord. We found that the deviations between the fractional extension distributions predicted by an asymptotic theory and those observed experimentally, are not due to a breakdown of the theory, even for experimental conditions which typically do not strictly satisfy the asymptotic limits of the theory. This motivated a closer inspection of the theories to determine a missing link between theory and experiment. Finally, by studying a recently generated dataset of fractional extensions spanning a wide range of the experimental parameter space, we were able to isolate this missing link as the effect of long-range electrostatics in the system which are typically ignored in the simplified theories, wherein the DNA is assumed as a neutral polymer confined in a channel of a reduced effective channel size. We believe that our findings within this dissertation will provide a better understanding of confined polymers and, in particular, the nanochannel confined DNA system used in genome mapping, as well as provide new directions of study in the future.
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    Data and code supporting: Simulations corroborate telegraph model predictions for the extension distributions of nanochannel confined DNA
    (2019-08-12) Bhandari, Aditya Bikram; Dorfman, Kevin D; dorfman@umn.edu; Dorfman, Kevin D; Dorfman
    Hairpins in the conformation of DNA confined in nanochannels close to their persistence length cause the distribution of their fractional extensions to be heavily left skewed. A recent theory rationalizes these skewed distributions using a correlated telegraph process, which can be solved exactly in the asymptotic limit of small but frequent hairpin formation. Pruned-enriched Rosenbluth method simulations of the fractional extension distribution for a channel-confined wormlike chain confirm the predictions of the telegraph model. Remarkably, the asymptotic result of the telegraph model remains robust well outside the asymptotic limit. As a result, the approximations in the theory required to map it to the polymer model and solve it in the asymptotic limit are not the source of discrepancies between the predictions of the telegraph model and experimental distributions of the extensions of DNA during genome mapping. The agreement between theory and simulations motivates future work to determine the source of the remaining discrepancies between the predictions of the telegraph model and experimental distributions of the extensions of DNA in nanochannels used for genome mapping.
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    Data for: Extension distribution for DNA confined in a nanochannel near the Odijk regime
    (2019-09-19) Chuang, Hui-Min; Reifenberger, Jeff G.; Bhandari, Aditya Bikram; Dorfman, Kevin D; dorfman@umn.edu; Dorfman, Kevin D.; University of Minnesota Dorfman Research Lab
    DNA confinement in a nanochannel typically is understood via mapping to the confinement of an equivalent neutral polymer by hard walls. This model has proven to be effective for confinement in relatively large channels where hairpin formation is frequent. An analysis of existing experimental data for Escherichia coli DNA extension in channels smaller than the persistence length, combined with an additional dataset for lambda -DNA confined in a 34 nm wide channel, reveals a breakdown in this approach as the channel size approaches the Odijk regime of strong confinement. In particular, the predicted extension distribution obtained from the asymptotic solution to the weakly correlated telegraph model for a confined wormlike chain deviates significantly from the experimental distribution obtained for DNA confinement in the 34 nm channel, and the discrepancy cannot be resolved by treating the alignment fluctuations or the effective channel size as fitting parameters. We posit that the DNA-wall electrostatic interactions, which are sensible throughout a significant fraction of the channel cross section in the Odijk regime, are the source of the disagreement between theory and experiment. Dimensional analysis of the wormlike chain propagator in channel confinement reveals the importance of a dimensionless parameter, reflecting the magnitude of the DNA-wall electrostatic interactions relative to thermal energy, which has not been considered explicitly in the prevailing theories for DNA confinement in a nanochannel.
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    Data from: Evaluation of Blob Theory for the Diffusion of DNA in Nanochannels
    (2018) Gupta, Damini; Bhandari, Aditya Bikram; Dorfman, Kevin D
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    A simple model for the wall depletion length of nanoconfined DNA (preprint)
    (2018-05-17) Bhandari, Aditya Bikram; Reifenberger, Jeffrey G; Chuang, Hui-Min; Cao, Han; Dorfman, Kevin D