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Equilibrium properties of DNA and other semiflexible polymers confined in nanochannels.

机译:限制在纳米通道中的DNA和其他半柔性聚合物的平衡特性。

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摘要

Recent developments in next-generation sequencing (NGS) techniques have opened the door for low-cost, high-throughput sequencing of genomes. However, these developments have also exposed the inability of NGS to track large scale genomic information, which are extremely important to understand the relationship between genotype and phenotype. Genome mapping offers a reliable way to obtain information about large-scale structural variations in a given genome. A promising variant of genome mapping involves confining single DNA molecules in nanochannels whose cross-sectional dimensions are approximately 50 nm. Despite the development and commercialization of nanochannel-based genome mapping technology, the polymer physics of DNA in confinement is only beginning to be understood.;Apart from its biological relevance, DNA is also used as a model polymer in experiments by polymer physicists. Indeed, the seminal experiments by Reisner et al. (2005) of DNA confined in nanochannels of different widths revealed discrepancies with the classical theories of Odijk and de Gennes for polymer confinement.;Picking up from the conclusions of the dissertation of Tree (2014), this dissertation addresses a number of key outstanding problems in the area of nanoconfined DNA. Adopting a Monte Carlo chain growth technique known as the pruned-enriched Rosenbluth method, we examine the equilibrium and near-equilibrium properties of DNA and other semiflexible polymers in nanochannel confinement. We begin by analyzing the dependence of molecular weight on various thermodynamic properties of confined semiflexible polymers. This allows us to point out the finite size effects that can occur when using low molecular weight DNA in experiments. We then analyze the statistics of backfolding and hairpin formation in the context of existing theories and discuss how our results can be used to engineer better conditions for genome mapping. Finally, we elucidate the diffusion behavior of confined semiflexible polymers by comparing and contrasting our results for asymptotically long chains with other similar studies in the literature.;We expect our findings to be not only beneficial to the design of better genome mapping devices, but also to the fundamental understanding of semiflexible polymers in confinement.
机译:下一代测序(NGS)技术的最新发展为低成本,高通量的基因组测序打开了大门。但是,这些进展也暴露了NGS无法跟踪大规模的基因组信息,这对于理解基因型和表型之间的关系极为重要。基因组作图提供了一种获取有关给定基因组中大规模结构变异信息的可靠方法。基因组作图的一个有希望的变体涉及将单个DNA分子限制在横截面尺寸约为50 nm的纳米通道中。尽管基于纳米通道的基因组作图技术已经发展和商业化,但人们对封闭DNA的高分子物理学的了解才刚刚开始。除其生物学意义外,DNA还在高分子物理学家的实验中用作模型高分子。确实,Reisner等人的开创性实验。 (2005年),DNA被限制在不同宽度的纳米通道中,揭示了与Odijk和de Gennes的经典理论在聚合物限制方面的差异。;摘自Tree(2014)的结论,该论文解决了许多关键的突出问题在纳米约束DNA领域。我们采用一种称为“修剪浓缩的Rosenbluth方法”的蒙特卡洛链增长技术,研究了纳米通道限制中DNA和其他半柔性聚合物的平衡和接近平衡性质。我们首先分析分子量对受限半柔性聚合物各种热力学性质的依赖性。这使我们指出了在实验中使用低分子量DNA时可能发生的有限大小效应。然后,我们在现有理论的背景下分析反向折叠和发夹形成的统计数据,并讨论如何将我们的结果用于设计基因组作图的更好条件。最后,我们通过将渐近长链的结果与文献中的其他类似研究进行比较和对比来阐明受限的半柔性聚合物的扩散行为。;我们希望我们的发现不仅有益于设计更好的基因组作图设备,而且对半柔性聚合物的基本了解。

著录项

  • 作者

    Muralidhar, Abhiram.;

  • 作者单位

    University of Minnesota.;

  • 授予单位 University of Minnesota.;
  • 学科 Materials science.;Chemical engineering.;Biophysics.;Genetics.
  • 学位 Ph.D.
  • 年度 2016
  • 页码 242 p.
  • 总页数 242
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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