Date on Master's Thesis/Doctoral Dissertation

12-2025

Document Type

Doctoral Dissertation

Degree Name

Ph. D.

Department

Chemical Engineering

Degree Program

Chemical Engineering, PhD

Committee Chair

Jaeger, Vance

Committee Member

Borchman, Douglas

Committee Member

Berson, R. Eric

Committee Member

Fu, Xiao-An

Author's Keywords

Molecular dynamics simulation; tear film lipid layer; dry eye syndrome; lipid order; miRNA adsorption

Abstract

Molecular dynamics (MD) simulation is an important tool in biochemical sciences for studying complex molecular processes and interfacial interactions at the molecular level. Biological interfaces play key roles in processes such as ocular lubrication and biomolecular adsorption. This dissertation studies interfacial phenomena involving two distinct yet conceptually related systems: the tear film lipid layer (TFLL) at the air–water interface at the surface of the human eye, and RNA adsorption on silica surfaces. These studies provide insight into how interfacial composition, structure, and environmental conditions affect larger-scale behavior. Atomistic MD simulations were used to model the TFLL. The TFLL is essential for maintaining ocular surface stability and preventing drying. Models of healthy, diseased, and compositionally altered TFLLs were created to study how lipid composition affects structural organization and biophysical properties like surface tension, lipid ordering, and diffusion. The simulations reproduced experimentally observed behaviors, validating the accuracy and usefulness of the models. Results showed that reduced concentrations of cholesteryl esters and polar lipids in dysfunctional TFLLs impair optimal properties. TFLL simulations uncover the molecular basis of dry eye disease, help explain phenomena described in the scientific literature, and inform potential therapies. A second set of MD simulations examined RNA-silica interactions by studying the adsorption of a 21-nucleotide microRNA (miRNA-21) under different pH and ionic conditions. Using parallel tempering metadynamics in the Well-Tempered Ensemble (PT-MetaD-WTE), simulations captured transitions between adsorbed, desorbed, compact, and extended RNA states. The results revealed that salt concentration and cation type strongly influence adsorption through RNA–silica and water–ion interactions. Acidic conditions reduced binding, while higher ionic strengths enhanced adsorption, clarifying how physicochemical factors control biomolecule–surface affinity. The results inform the development of silica-based bio-preservation technologies. Overall, these projects demonstrate the power of MD simulations to reveal structure–function relationships at biological interfaces. The findings connect molecular-level interactions with experimentally observable behavior, providing a basis for designing better ocular therapies and optimized biomaterial surfaces for RNA applications.

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