Design Rules Linking Tear Film Lipid Composition to Mechanical Stability and Lubrication of the Eye

Dry Eye Disease affects over thirty million Americans and imposes an annual economic burden exceeding $55 billion in healthcare costs and lost productivity. Despite its clinical importance, the fundamental principles connecting the molecular composition of this lipid layer to its mechanical performance remain poorly understood. Most current treatments address symptoms rather than the underlying causes of film instability. This research project will identify the design rules that govern how tear film lipid composition controls stability, lubrication, and resistance to mechanical failure. The findings will provide a scientific foundation for developing targeted therapies for Dry Eye Disease. They will also guide the creation of bio-inspired lubricating materials for medical technologies such as long-wear contact lenses, ocular implants, and artificial joint systems, contributing to United States leadership in biotechnology. The project includes a hands-on outreach module, The Amazing Engineering of Your Eye, designed to introduce kindergarten through K12 students to core concepts in biomechanics and biomedical engineering. University students will receive training in advanced biophysical measurement methods, building a skilled and interdisciplinary workforce for the biotechnology sector. This research project seeks to establish a quantitative, mechanism-based framework linking the molecular architecture of the tear film lipid layer to its interfacial biomechanical and tribological performance. Although the biochemical composition of the tear film has been extensively cataloged, the causal relationships between nonpolar lipid attributes and the resulting mechanical stability, adhesion, and frictional response remain unresolved. Three coordinated research objectives address this gap through the lens of interfacial biomechanics and mechanobiology. Objective 1 will determine how structural features of major nonpolar lipid classes, wax esters, cholesterol esters, and triacylglycerols, regulate thermodynamic stability and interfacial viscoelasticity using Langmuir trough isotherms and dilatational rheology. Objective 2 will map the molecular-scale adhesive energy landscape between the lipid layer and the lid-margin glycocalyx using the Surface Forces Apparatus, enabling simultaneous measurement of piconewton-scale normal forces and sub-nanometer separations via multiple-beam interferometry. Objective 3 will identify the dominant tribological mechanisms responsible for ultra-low friction under high-speed cyclic shear and test the distinct biomechanical roles of lipid classes. These studies will produce the quantitative force maps for this biologically critical interface and establish predictive structure–function relationships connecting lipid molecular architecture to interfacial mechanics, adhesion, and lubrication. The findings will enable a new mechanistic foundation for understanding biomechanical failure of biological thin films, with implications for ocular surface mechanobiology, tribology, and the rational engineering of bio-inspired lubricating interfaces. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria. NSF Award ID: 2545214 | Program: 01002627DB NSF RESEARCH & RELATED ACTIVIT | Principal Investigator: Younjin Min | Institution: University of California-Riverside, RIVERSIDE, CA | Award Amount: $398,609 View on NSF Award Search: https://www.nsf.gov/awardsearch/show-award/?AWD_ID=2545214 View on Research.gov: https://www.research.gov/awardapi-service/v1/awards/2545214.html