Using Brownian Dynamics Simulation Method to Analyze the Influence of Positive Charge Density and Solution Ionic Strength on the Behavior of Adsorbed DNA on Lipid Bilayers
| Autor: | Ming-Yi Chang, 張名熠 |
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| Rok vydání: | 2018 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 106 It is observed in the experiments that when DNA is adsorbed on a positive charged lipid bilayer, its behavior follows Rouse model in two dimension. Moreover, the charge density of the lipid bilayer and the ionic strength of the solution have a significant influence on the behavior of adsorbed DNA. In our experimental observations, the diffusivity and the radius of gyration of the adsorbed DNA with low charge density of lipid bilayers and high ionic strength solution are in good agreement with the theoretical prediction. However, DNA behavior greatly deviates from the theoretical prediction when the measurement is taken at the lipid bilayer with high positive charge density or in the solution with low ionic strength. We supposed that this deviation is related to the change of the local composition of the lipid bilayer due to electrostatic interaction after DNA is adsorbed. Therefore, we intend to parse it with the help of simulation. We used Brownian dynamics (BD) with bead-spring model to simulate the behavior of DNA adsorbed on positively charged lipid bilayers. We first set up a fixed lipid bilayer model with a uniform charge density and a local heterogeneous model. In the local heterogeneous lipid bilayer model, there existed many sticky points and sub-diffusion is also observed. However, normal diffusion DNA was not observed. We speculated that the normal diffusion of adsorbed DNA comes from the movement of the lipids. Therefore, we used beads with different charges to simulate the lipids in two-dimensional bilayer. This model, called mobile lipid bilayer model, also allows the interaction between DNA and lipids, and therefore local heterogeneity can naturally occur. Under a constant ionic strength, the DNA conformation changes from partial adsorption to complete adsorption on the surface of the lipid bilayer as the charge density of the lipid bilayer increases. Furthermore, DNA radius of gyration increases but DNA diffusivity decreases. However, after the surface charge density is high enough to completely adsorb the DNA, increasing the charge density of the lipid bilayer does not have much effect on the DNA diffusivity and its radius of gyration. Under constant lipid charge density, we found that decreasing ionic strength has similar effects as increasing lipid charge density in our simulations. These results were quite different from those observed in our experiments, and the sub-diffusion observed in the experiment did not occur in this model. From the simulation results, we have deduced that (1) the normal diffusion behavior of the adsorbed DNA comes from the movement of the lipids and (2) the local heterogeneity in system with mobile lipids does not restrict DNA motion and not cause the sub-diffusion. (3) Fixed charges can form sticky points and induce sub-diffusion. Combining above simulation analysis with the phenomenon observed in the experiments, we suspected that the surface defects might form several local energy wells which confine DNA motion. To simulate the effect of these energy wells, we added several fixed charge points without volume to the mobile lipid bilayer model to mimic the local energy well. By changing the charges of the energy well, the adsorbed DNA exhibits different degrees of sub-diffusion behavior. Moreover, we found that DNA is confined between fixed charges and cannot reach its equilibrium conformation at low ionic strength condition, consistent with our observation in experiments. Therefore, the simulation results support our postulation that there are potential wells existing on the lipid bilayers. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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