Interaction between polyelectrolytes and oppositely charged substances results in various self assembled structures commonplace in industrial settings, health care, and biology. While there is a large body of experimental work on polyelectrolyte complexation, much lagged behind is development of a reliable theoretical tool to describe the underlying structure and thermophysical properties. The theoretical predictions are important not only for engineering applications but also for understanding fundamental biological processes that involve association of oppositely charged biomacromolecules. The proposed research seeks to develop predictive models useful for quantifying structure and thermodynamic stability of polyelectrolyte complexes from a molecular perspective. The theoretical models will be validated with results from molecular simulations and well characterized experimental systems. A case study is also proposed to apply the theoretical tools for understanding genome packaging in viral capsids.
Intellectual merit:
The theoretical techniques to be used in this research are built upon recent work in the PI's group in development and application of classical density functional theory (DFT). DFT provides a unifying computational tool for describing the microscopic structure and interfacial behavior of complex molecular systems. Preliminary investigations have demonstrated that it is able to capture both the local packaging and long range electrostatic and intra chain correlations essential for a successful description of strongly charged polyelectrolyte systems. The planned research focuses on development of complementary molecular models for investigating the structure and phase transitions of polyelectrolyte complexes. If successful, accomplishments from this work may open new avenues for understanding diverse molecular self assembly processes and thereby will transform industrial design and practice of both synthetic and natural polyelectrolyte systems.
Broader impacts: The generic nature of the theoretical techniques proposed in this work promises applications not only to polyelectrolyte systems but also to the broader fields of complex fluids. In particular, development of advanced computational methods may have unusual impacts in fundamental research toward understanding the molecular basis of viral replication cycle that often entails strong interactions of DNA/RNA chains with oppositely charged polypeptides or proteins. Such understanding is essential for identification of potential drug targets for treatment of virus induced contagious diseases and for formulation of efficient gene/biopharmaceuticals health care delivery systems.
This project will provide opportunity for young scientists to gain interdisciplinary research experience and motivate their career interests in molecular modeling and engineering. In addition to supporting one senior graduate student toward his/her advanced degree, this project will recruit at least two undergraduate students from the University Honors Program (UHP) by offering research based thesis projects. Based on the introductory materials related to this research, the PI plans to prepare lectures and special seminars to introduce recent developments in viral self assembly and gene delivery. In addition to UHP, the introductory materials will also be used for the university FastStart summer academy program, designed for high-school students who aspire to biomedical and engineering careers
This project seeks to develop molecular models and theoretical methods useful for predicting the structure and thermodynamic properties of polyelectrolytes and their interactions with oppositely charged polymers, surfactants or surfaces in an aqueous environment. In addition to theoretical developments and validation with experimental data and molecular simulations, the new theoretical approaches were applied to genome packaging in viral capsids as a model system. Over the entire duration of NSF support, this project results in 28 peer-reviewed publications, 2 PhD theses, and numerous technical presentations at national and international meetings. The generic nature of the theoretical techniques developed in this work promises broad applications not only to polyelectrolyte systems but also to other fields of complex fluids and biological systems. For example, thermodynamic properties are important for utilizing polyelectrolyte complexes in ecology, biotechnology, medicine and pharmaceutical technology. In particular, the polyelectrolyte complexes have great potential in the design of novel drug delivery systems. The advanced computational methods developed in this work will have unusual impacts in fundamental research toward understanding the molecular basis of viral replication that often entails strong interactions of DNA/RNA chains with oppositely charged polypeptides or proteins. Such understanding is essential for identification of potential drug targets for treatment of virus-induced contagious diseases and for formulation of efficient gene/biopharmaceuticals delivery systems. This project provided training opportunities for young scientists to gain interdisciplinary research experience and cultivate their career interests in computational molecular engineering. In addition to supporting graduate students, it offered research experiences for a large number of undergrads including those with socioeconomically disadvantaged backgrounds. Near a dozen undergrads had participated in the research and many are female students from underrepresented ethnic groups. The NSF-sponsored research consists of an essential component of two PhD dissertations, and the research activities contribute to the professional development for both the graduate students and the postdoctoral fellows.
