(4cr) Interfacial and Rheological Properties of Ocular Epithelia

My thesis work focuses on how glycoproteins can alter the interfacial properties of epithelial cell layers from a rheological perspective, aiming to understand the underlying pathology and seek solutions for dry eye diseases. Specifically, a combination of fluorescent microscopy, contact angle hysteresis, and rheometry was applied to investigate the mechanisms behind mucin deficiency and the increased frictional damages at the ocular surfaces.

To perturb the glycoproteins tethered to the cell membrane, I initiated a collaboration with Professor Carolyn Bertozzi’s group and utilized a recently purified mucinase, StcE, that can cleave off membrane tethered mucins. With the mucin-deficient cell model, I tested the adhesive forces at healthy and diseased corneal/conjunctival interface and revealed that a sustainable lubrication at the ocular surface requires optimized surface chemistry and surface morphology. In addition, mucinase can successfully increase the adhesion at the cell-cell interface, and the addition of glycoproteins can rescue the native lubrication function. The results suggest that mucin-deficiency-induced dry eye disease might be reversible with topical treatments, and the corneal surface morphology can complement current investigations on dry eye diseases of unknown origin.

A further study on the interfacial properties of corneal epithelium was initiated by a surprising finding that epithelial cell layers exhibited delamination behaviors in captive bubble experiments. The conventional Schultz’s method was modified to measure the surface tension of corneal and conjunctival epithelium. Through the force balance at the contact line, the cell-cell adhesion force and the cell-substrate adhesion force were directly calculated. The results confirmed that cytoskeleton, instead of cell-cell junction, give rise to epithelial integrity. In addition, a delicate balance between cytoskeletal modulus, interfacial tension, and cell-substrate adhesion ensures stable and mobile epithelial cell layers.

Research Interests

In my future academic career, I would like to utilize my background in interfacial rheology and mucin biophysics to understand the pathology of epithelial diseases and engineer a precise medical solution in collaboration with clinicians and polymer chemists. The epithelium is the first line of defense in the human body, constantly resisting mechanical, chemical, and biological stresses from external environments. Though we understand the development of epithelium, epithelial diseases, including canker sores, keratitis, and Sjogren’s syndrome, remain challenging to tackle due to the intertwined biophysical and biochemical cues present at epithelial interfaces. The current mechanotransduction study focuses on the influence of substrate rheology, while the disparagingly different environments across epithelium tissues are often overlooked. I would like to explore how the changes across the epithelial interfaces, e.g., interfacial stress, viscosity, and chemical composition, can influence the mechanical and biological functions of epithelial tissues. To achieve this goal, conventional methods to study interfacial properties of synthetic materials need to be adapted to biological tissues. With my background in instrument building, I believe that further understanding of the interfacial properties of epithelial tissues can yield fruitful insights into the pathology of many epithelial diseases.

Teaching Interests

I firmly believe that the values of engineering courses are delivered most efficiently in a laboratory-based and project-oriented format. I have served as a TA for graduate-level fluid mechanics and rheology classes. Fluid mechanics is a foundational class for Chemical Engineering students. However, a heavy focus on the mathematical formulation sometimes clouds the beauty of the subject, and students with varied math backgrounds often find these classes hard to follow and have little practical use. I hope to design a fluid mechanics class in which students will build intuition of Navier-Stokes equation and appreciate the subject and its rich history. Furthermore, I would like to design a lab-based soft matter physics class through which students can learn to be proactive in observing and reflecting their daily life, be receptive of new ideas, practice critical thinking in all aspects of their life, and be open and strategic about exchanging their thoughts in their community.