UH Med Now

Consider the teardrop, a vital lubricant for the eye encased in a thin biomembrane called a surfactant, to ensure it does its job in the blink of an eye — lubricate the eyeball.  There is a similar surfactant that coats the alveoli in the lungs. When babies are born prematurely, there is insufficient surfactant so they are put on ventilators, which adds the risk for lung infections. The study of these surfactants naturally generated by the body is geared toward solving problems of the eyes, lungs, and lung issues caused by COVID-19. 

As the cover-scientist for Biophysical Journal’s February 1st, 2022, issue, Yi Zuo, PhD, – and the Zuo Lab – shared the results of a novel experimental method about the surface of a teardrop, called constrained drop surfactometry (CDS), to gain mechanistic insight into the tear film lipid layer (TFLL), also known as the outermost layer of the eyeball. This layer plays a crucial role in stabilizing the tear film by reducing surface tension and constraining water evaporation. For this experiment, the Zuo Lab, also known as the Laboratory of Biocolloids and Biointerfaces (LoBB), generated high-fidelity biophysical simulations of the TFLL under physiologically relevant conditions.

An artist’s rendition of constrained drop surfactometry, studying the biophysical and rheological properties of the tear film lipid layer. Zuo and coworkers have developed a novel in vitro model that allows high-fidelity biophysical simulations of the tear film lipid layer under physiologically relevant conditions.

“Interfacial rheology determines the viscoelastic properties of a thin-film material, such as the tear film [of eyes] and lung surfactant film. These properties are important to understand biomembranes under highly dynamic conditions, such as the respreads of a tear film on the ocular surface during a blink,” Zuo said. 

Zuo’s initial interests in mechanical engineering went into a tangent focused on surface thermodynamics and on the way he collected post-doctoral fellowships in biochemistry, chemistry, and OBGYN at the University of Western Ontario. He earned his PhD in mechanical engineering at the University of Toronto in 2006. Prior to that he earned his BS and MS, both in mechanical engineering, at the University of Science and Technology Beijing.

Following his six years of professorships at the University of Hawai’i in the Mechanical Engineering department, Zuo joined the faculty at the John A. Burns School of Medicine (JABSOM) in 2018 as an adjunct professor in the Pediatrics department, and as graduate faculty in the Cell & Molecular Biology department. Who would have thought that a mechanical engineer could end up in medicine? 

“Surface thermodynamics is a highly interdisciplinary research area. Particularly, in our  LoBB, we work on research areas where engineering, physics, chemistry, biology, and medical science meet,” Zuo said. “I was trained as an interdisciplinary researcher during my PhD in engineering and postdoc in biochemistry and OBGYN.” 

Zuo has developed multidisciplinary graduate courses, such as Interfacial Phenomena and Statistical Thermodynamics – not traditional engineering curriculum, but that which broadens the scope of student learning. Zuo and his team in the LoBB were recognized by the 2020 Norman Edmund Inspiration Award for its multidisciplinary and collaborative lab culture: 

“Dr. Zuo tries to invest in undergraduate and graduate students’ educations. He does this by co-authoring published papers with his students in order to give them recognition for their work and bolster their credibility in their field. Additionally, Dr. Zuo has structured his lab so that his researchers can pursue their own path of studies, encouraging them to continue to do what they are good at and enjoy themselves. As a result, students are not only able to foster experience in a field in which they are invested, it also helps to prevent burnout in a new generation of scientists.

“While the clinical applications of the research done by the laboratory lend themselves to students continuing on into the medical field, there is not one set path for alumni of the Laboratory of Biocolloids and Biointerfaces. Many students pursue a career in medicine, some go straight into industry jobs, and some remain in academia. The diversity of career options is a marked success of the laboratory and Dr. Zuo’s investment in young scientists as they pursue life paths about which they are passionate.”

The major research area in the LoBB is the study of lung surfactant, a lipid and protein mixture synthesized by lung cells. According to Zuo, a unique feature of lung surfactant is its extremely low surface tension. By reducing surface tension of our lungs, lung surfactant helps us breath with ease.

Due to the lack of surfactant, premature infants suffering from RDS exhibit alveolar collapse and decreased lung compliance, which impairs gas exchange in the lung. The inserts show the comparison of normal and collapsed alveolar tissues, which show the reduced alveolar capacity and increased alveolocapillary barrier in the underdeveloped lung. Courtesy graphic.

One of the final touches to a baby in the womb occurs in the lungs, where the delicate alveoli are lightly coated with stretchy surfactant cells, making inhaling (expanding) and exhaling (contracting) easy. Unfortunately, babies born prematurely do not have that stretchy advantage and often will spend weeks on a ventilator that forces oxygen into the lungs. Without sufficient surfactant cells to help the alveoli stretch for breaths, the use of ventilators makes preemies vulnerable to lung inflammation and fluid accumulation, both of which could be fatal. The Zuo LoBB is studying lung surfactant as a carrier to deliver anti-inflammatory drugs, such as corticosteroids, directly to the lungs. Such a therapy helps minimize the adverse neurodevelopmental effect of corticosteroids.

In an article about the Zuo Lab at edmundoptics.com, “…lung surfactant research involves studying the surface tension of purified animal lung surfactants and how they act in a human respiratory simulation upon compression and expansion of the surfactant film. The main benefactors of the research would be infants in a neonatal intensive care unit (NICU) setting as premature infants are susceptible to respiratory distress syndrome.”

Building off of that research, Zuo and his lab are now studying the possibility of using lung surfactant as a supportive therapy to treat patients with COVID-19. Many research organizations around the world, such as the Cincinnati Children’s Hospital Medical Center, Canada’s Lawson Health Research Institute, and Denmark’s National Research Centre for the Working Environment, are using the system developed by the LoBB to simulate respiration and study human response to hazardous aerosols that pollute the atmosphere. 

By Paula Bender, UH Med Now

Dr. Yi Zuo, Adjunct Professor, Department of Pediatrics, John A. Burns School of Medicine (JABSOM)
Graduate Faculty, Department of Cell and Molecular Biology, JABSOM. Professor, Department of Mechanical Engineering, College of Engineering
Courtesy photo.