Merina Jahan

Date of Award

Fall 2019

Document Type

Open Access Dissertation


Chemical Engineering

First Advisor

Mark J. Uline


Current research trends throughout the world focus on designing intelligent materi- als and systems for diverse applications in all courses of life. Biomaterials research encompasses a major part in this revolution due to the increased effort in fulfilling unmet medical needs to treat complex physiological and neurodegenerative disorders. Polymers play inevitable roles in these research endeavors for their ubiquitous pres- ence in biological systems. Therefore, it is crucial to understand how the polymeric molecules interact within diverse biological environments, to efficiently engineer them for various drug delivery and biosensing systems. The use of experimental design and selection of different polymers for diverse applications alone is an arduous task. Hence, theoretical studies on these biological systems become important starting points for projects that have previously been only studied with experimental techniques. Using theory can make the job easier for researchers in biomedical engineering by both coa- lescing large bodies of experimental data into conceptual frameworks and narrowing down a parameter search space.

Along this line, our research focuses on theoretical molecular level modeling of complex polymeric molecules, both biological and synthetic, for drug delivery and biosensing applications. The objective is to design new polymeric systems based on their structural, thermodynamic and physicochemical properties to help enhance the experimental design. This research work uses a Self Consistent Field Theory (SCFT) based approach for different applications involving polymers, that are teth- ered and electrolytic in nature. The molecular theory studies the thermodynamic and structural behavior of the polymers as a function of their molecular composition and physicochemical environments. This theory is able to perform systematic thermody- namic calculations at low computational cost, while including a detailed molecular description of the molecules in the system. The competition of all relevant molecu- lar interactions, such as electrostatics, van der Waals, thermodynamic and chemical equilibrium is described in this model.

The first study involves elucidating the behavior of ssDNA aptamers in different biological environments. Our study suggests that the structure of the aptamer chains varies significantly due to charge regulation effects, in response to changes in salt concentration, types and ionic strength of salt and density of the aptamer brush. The understanding gained from this study can help to facilitate aptamer selection process against specific target molecules.

Our second study inquires the property changes of ssDNA aptamers in presence of divalent metal cations and quantifies the number of metal ions bound to the ap- tamer chains. The results imply that the ion cloud around the oligomers is uniformly distributed in different sequences and reinforces the dominance of non-specific elec- trostatic attraction between the nucleobases and the cations as the driving force for cation-binding. Our results also show that the ionic strength has a more prominent effect on the structure and properties of the oligomer brushes when they are densely grafted, compared to their sparsely grafted counterparts. In its current state, this model can serve as a foundation for field theoric studies of more complex systems to dissect the ion binding scenario around aptamers and single stranded nucleic acids.

The third study in this dissertation analyses the behavior of a pH responsive polymer (PMAA), complexed with a small molecule drug (PD166793), and grafted to a nanoparticle surface, to design a controlled and sustained drug delivery system for enhanced cardiovascular repair. The molecular theory results elucidate the reasons for why the polymer shows poor drug binding at physiological pH and higher drug binding at acidic pH. Based on these findings, we present a proof of concept of how the molecular level understanding of this system can be leveraged to increase drug binding at physiological pH by adding a strong polyelectrolyte to the system. This study can aid in designing new drug delivery systems with improved efficacy and sustainability, not only for cardiovascular diseases, but also for other critical and time-sensitive diseases.