Download the full-sized PDF of Molecular Dynamics Simulations of Polyethylenimine Mediated Nucleic Acid Complexation with Implications for Non-viral Gene DeliveryDownload the full-sized PDF



Permanent link (DOI):


Export to: EndNote  |  Zotero  |  Mendeley


This file is in the following communities:

Graduate Studies and Research, Faculty of


This file is in the following collections:

Theses and Dissertations

Molecular Dynamics Simulations of Polyethylenimine Mediated Nucleic Acid Complexation with Implications for Non-viral Gene Delivery Open Access


Other title
Nucleic Acid
All-atom Simulation
Molecular Dynamics
Non-viral Gene Delivery
Lipid Substitution
Type of item
Degree grantor
University of Alberta
Author or creator
Sun, Chongbo
Supervisor and department
Tang, Tian (Mechanical Engineering)
Examining committee member and department
Carey, Jason (Mechanical Engineering)
Tang, Tian (Mechanical Engineering)
Wang, Yongmei (Chemistry, University ofMemphis)
Uludag, Hasan (Chemical and Materials Engineering)
Bhattacharjee, Subir (Mechanical Engineering)
Department of Mechanical Engineering

Date accepted
Graduation date
Doctor of Philosophy
Degree level
Gene therapy is a promising therapeutic technique that involves delivering nucleic acids into cells. Polycations have evolved into a major category of gene carriers. Polyethylenimine (PEI) is one of the most effective polycationic carriers. Furthermore, modifying PEI with certain lipophilic moieties was found to greatly improve its performance. Despite the great potential of PEI-based carriers,the understanding of complexation of nucleic acids with PEIs is still lacking at the atomistic level. In addition, the mechanisms for the beneficial effects of lipid modification remain unclear and to be probed. In this dissertation, a series of molecular dynamics simulations were performed to investigate the PEI/nucleic acids complexation. We started our simulations from single DNA interacting with single PEI and investigated eight 600 Da PEIs with four different architectures and at two protonation ratios. We found that for these low molecular weight PEIs, compared with the protonation state, the degree of branching has a smaller effect on binding. We then increased the size of the system to incorporate one DNA with multiple PEIs and increased the molecular weight of the PEIs to 2 kDa. Unlike in the case of 600 Da PEIs, the simulations revealed distinct binding modes of branched and linear PEIs to DNA, demonstrating that the molecular weight of PEI is an important factor in PEI/DNA complexation. Following this simulation, complexation/aggregation of DNA molecules medicated by PEIs was studied by simulating multiple DNA molecules with excessive PEIs. We found that native PEIs condense DNA through two mechanisms - polyion bridging and electrostatic screening of the DNA charges. The effects of lipid substitution on polycation mediated nucleic acids aggregation was then explored by adopting lipid-modified PEIs in the simulations of multiple DNAs and siRNAs complexation. The lipid moieties were found to associate significantly with one another, which provides another mechanism of aggregating nucleic acids and stabilizing the formed polyplexes. The effects of lipid length and substitution level on the formed polyplexes were also investigated. This dissertation will advance the understanding of PEI/nucleic acids polyplexes at atomistic level. Moreover, the methodology adopted suggests a framework for systematically evaluating polycationic carriers using molecular simulations.
Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.
Citation for previous publication
C. Sun, T. Tang, "Study the role of polyethylenimine as gene delivery carrier using molecular dynamics simulations", J. Adhesion Sci. Tech., 2012, In Press. DOI:10.1080/01694243.2012.693830C. Sun, T. Tang, H. Uludag, J. Cuervo, "Molecular dynamics simulations of DNA/PEI complexes: Effect of PEI branching and protonation state", Biophys. J., 2011, 100 (11), p2754-2763.C. Sun, T. Tang, H. Uludag, "Molecular Dynamics Simulations for Complexation of DNA with 2 kDa PEI Reveal Profound Effect of PEI Architecture on Complexation", J. Phys. Chem. B, 2012, 116 (8), p2405-2413.C. Sun, T. Tang, H. Uludag, "Molecular Dynamics Simulations of PEI Mediated DNA Aggregation", Biomacromolecules, 2011, 12 (10), p3698-3707.C. Sun, T. Tang, H. Uludag, "Probing the Effects of Lipid Substitution on Polycation Mediated DNA Aggregation: A Molecular Dynamics Simulations Study", Biomacromolecules, 2012, 13 (9), p2982-2988.C. Sun, T. Tang, H. Uludag, "A Molecular Dynamics Simulation Study on the effect of Lipid Substitution on Polyethylenimine Mediated siRNA Complexation", Biomaterials, 2013, In Press. DOI:10.1016/j.biomaterials.2013.01.011

File Details

Date Uploaded
Date Modified
Audit Status
Audits have not yet been run on this file.
File format: pdf (Portable Document Format)
Mime type: application/pdf
File size: 8810251
Last modified: 2015:10:12 12:52:35-06:00
Filename: Sun_Chongbo_Spring2013.pdf
Original checksum: 2d2ee9b5b3ef03b7a7dfbbae5f3a07c7
Well formed: true
Valid: false
Status message: Invalid page tree node offset=4092
File title: thesis.dvi
Activity of users you follow
User Activity Date