With the recent completion of the Human Genome Project and the announcement of the $1000 Genome Race in 2003, the interest for developing faster and cheaper sequencing technologies is continuously growing. Nanopore sequencing offers one of the most promising new ideas. This method consists in reading DNA as it passes through a small aperture perforated through a membrane; a technique similar to decoding a magnetic tape in a tape player. The process of linearly moving a flexible chain from one side of a small channel to the other is called polymer translocation. However, the physics behind this process is still not well understood. During the last ten years, theorists proposed several scaling laws in order to describe this problem and explain experimental observations. The goal of this thesis is to shed light on some of these interesting theoretical predictions.
One of the most important questions addressed in this thesis is the role of the hydrodynamic interactions in the polymer translocation process. Even though the impact of such interactions have been theoretically considered, they are neglected in most simulation models. One of our aims in this thesis is to look at the implications of increasing the pore diameter in the presence of hydrodynamic interactions. We use Molecular Dynamics simulations with explicit solvent particles to generate unbiased translocation events in order to characterize the screening of the hydrodynamic interactions by the membrane and to test the hypothesis that polymer translocation is a quasi-equilibrium process. The latter question is quite fundamental since this assumption is at the origin of most theoretical approaches.
Another major goal of this thesis is to clarify the nature of the transition between the two translocation regimes dominated by the pore-polymer friction and the hydrodynamic drag of the subchains outside the channel, respectively. However, such an investigation requires the ability to simulate translocation events with a very wide range of polymer lengths. We thus propose a new Monte Carlo method based on a one-dimensional random-walk representation of the translocation problem that can easily be used to study chain lengths as large as 10' monomers. This model works in conjunction with an exact calculation technique to compute the key results of the translocation events such as the probability to occur and the average time duration. It is used to validate previous and make new theoretical predictions about translocation dynamics as the polymer and channel lengths are varied. It is also applied to the study of chain heterogeneity effects.
| Identifer | oai:union.ndltd.org:uottawa.ca/oai:ruor.uottawa.ca:10393/29726 |
| Date | January 2008 |
| Creators | Gauthier, Michel G |
| Publisher | University of Ottawa (Canada) |
| Source Sets | Université d’Ottawa |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | 131 p. |
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