(357aw) Understanding interfacial composition and structure of lipid-based surfactant monolayers for treatment of pulmonary diseases

I have experience in academic and industrial research of soft materials and interfacial phenomena motivated primarily by biomedical, beauty, and home care applications. I am inspired by the diverse design space and versatility of soft materials and the ability of surfactants to drive the formation and stabilization of structures in soft materials. My research interest is in investigating the relationship between the molecular composition and microstructure of a material in order to understand and optimize its macroscopic properties. My thesis research has an emphasis on visualizing and probing microstructures formed by surfactant mixtures at interfaces. For example, I’ve used a combination of fluorescence microscopy, interfacial rheology, and surface tension measuring techniques to study the effects of molecular composition on the structure and rheology of lung surfactant mixtures. In some of my additional research experiences, I’ve used a multitude of atomic, micro-, and macro-scale characterization techniques to study the effects of composition and fabrication method on the performance of consumer goods such as antiperspirants and hard surface cleaners, as well as the incorporation of functional proteins into nanostructured silica for electrochemical device applications. Going forward, I am interested in opportunities to utilize my interdisciplinary background to develop innovative, creative solutions for multi-length scale material design and optimization projects.

PhD Thesis Research

Complex fluid-fluid interfaces are ubiquitous in many industries such as biomedical, food, personal care and, petroleum. At fluid-fluid interfaces surface-active species adsorb to the interface, sometimes forming microstructures which give the interface its unique mechanical properties. Studying these interfacial properties is critical for understanding such materials and integrating into product designs. In this investigation, the study of lipid-containing surfactant monolayers is motivated by their relevance to the study and treatment of pulmonary diseases, such as acute respiratory distress syndrome (ARDS), neonatal respiratory distress syndrome (NRDS), and COVID-19. More specifically, much of this body of work focuses on lung surfactant (LS), the lipid-based surfactant layer at the air-water interface lining the alveoli inside the lung. The LS layer reduces surface tension and stabilizes the lung against collapse and overdistension, and is thus necessary for respiration. LS is said to be ‘inactivated’, meaning that it loses its ability to moderate surface tension to healthy levels, in ARDS [1]. However, the inactivation mechanism remains unknown. In this study we focus on the role of phospholipase (PLA₂) in LS inactivation, an enzyme known to be present in increased levels in the lungs of ARDS patients. PLA₂ hydrolyzes lipids such as DPPC into palmitic acid (PA) and lyso-PC (LPC) [2,3]. Since PA co-crystallizes with DPPC to form rigid, elastic domains [4], we hypothesize that PLA₂-catalyzed degradation establishes a stiff, heterogeneous rheology in the monolayer, which will impair LS function. Here we study the evolution of a DPPC monolayer forming a 2D gel-like network as it is degraded by PLA₂. Using interfacial microbutton microrheometry coupled with fluorescence microscopy, we track local rheology and morphology of the actively degrading monolayer. These results are compared to monolayers with fixed amounts of DPPC and its degradation products, simulating the evolving composition of the degrading monolayers.

References:

[1] Notter, R. Lung Surfactants: Basic Science and Clinical Applications. 1; Lenfant C., Eds.; Lung Biology in Health and Disease; Marcel Dekker, Inc.: New York, 2000; Vol. 149; 233-247.

[2] Thompson, B. T.; Chambers, R. C.; Liu, K. D. N. Engl. J. Med. 2017, 377, 562-572.

[3] Nakos, G.; Kitsiouli, E. I., Tsangaris, I.; Lekka, M. E. Intensive Care Med. 1998, 24, 296-303.

[4] Ding, J.; Warriner, H. E.; Zasadzinski, J. A. Phys. Rev. Lett. 2002. 88, 1-4.