4.8 Review

Pulmonary Surfactant: A Mighty Thin Film


Volume -, Issue -, Pages -


DOI: 10.1021/acs.chemrev.3c00146



Ask authors/readers for more resources

Pulmonary surfactant plays a critical role in lung function by reducing lung alveoli surface tension. The prevailing belief of a compression-driven squeeze-out mechanism may be incorrect, and a new model suggests that an enriched film of saturated lipids is formed shortly after birth through an adsorption-driven sorting process. This proposed model is supported by biophysical evidence and should be further investigated to establish its physiological relevance.
Pulmonary surfactant is a critical component of lung function in healthy individuals. It functions in part by lowering surface tension in the alveoli, thereby allowing for breathing with minimal effort. The prevailing thinking is that low surface tension is attained by a compression-driven squeeze-out of unsaturated phospholipids during exhalation, forming a film enriched in saturated phospholipids that achieves surface tensions close to zero. A thorough review of past and recent literature suggests that the compression-driven squeeze-out mechanism may be erroneous. Here, we posit that a surfactant film enriched in saturated lipids is formed shortly after birth by an adsorption-driven sorting process and that its composition does not change during normal breathing. We provide biophysical evidence for the rapid formation of an enriched film at high surfactant concentrations, facilitated by adsorption structures containing hydrophobic surfactant proteins. We examine biophysical evidence for and against the compression-driven squeeze-out mechanism and propose a new model for surfactant function. The proposed model is tested against existing physiological and pathophysiological evidence in neonatal and adult lungs, leading to ideas for biophysical research, that should be addressed to establish the physiological relevance of this new perspective on the function of the mighty thin film that surfactant provides.


I am an author on this paper
Click your name to claim this paper and add it to your profile.


Primary Rating

Not enough ratings

Secondary Ratings

Scientific rigor
Rate this paper


Article Chemistry, Physical

Relative Dye Adsorption Method for Determining the Hydrophobicity of Nanoparticles

Guangle Li, Kacie K. H. Y. Ho, Yi Y. Zuo

Summary: The hydrophobicity of nanoparticles is a crucial property that influences their agglomeration state and toxicity, but there is currently no widely accepted standard method to characterize it. The relative dye adsorption method provides a more reliable technique for determining the hydrophobicity of NPs compared to traditional methods using hydrophobic or hydrophilic dyes.


Article Physiology

Menthol in electronic cigarettes causes biophysical inhibition of pulmonary surfactant

Lu Xu, Yi Yang, Jennifer Michelle Simien, Christopher Kang, Guangle Li, Xiaojie Xu, Ellinor Haglund, Rui Sun, Yi Y. Zuo

Summary: With the increasing prevalence of electronic cigarette use, it is important to understand the biological risks and pathophysiology of health conditions related to e-cigarettes, especially among youth. This study found that menthol, a flavoring used in e-cigarettes, played a predominant role in inhibiting the biophysical function of pulmonary surfactant.


Article Chemistry, Physical

S2 Subunit of SARS-CoV-2 Spike Protein Induces Domain Fusion in Natural Pulmonary Surfactant Monolayers

Xiaojie Xu, Guangle Li, Bingbing Sun, Yi Y. Zuo

Summary: The S2 subunit of the SARS-CoV-2 S protein inhibits the biophysical properties of pulmonary surfactant and induces microdomain fusion in the surfactant monolayer. These findings provide important insights into the mechanisms of surfactant-virus interactions and the development of surfactant replacement therapy for COVID-19.


Article Chemistry, Multidisciplinary

Mucus Penetration of Surface-Engineered Nanoparticles in Various pH Microenvironments

Yiyang Guo, Yubin Ma, Xin Chen, Min Li, Xuehu Ma, Gang Cheng, Changying Xue, Yi Y. Zuo, Bingbing Sun

Summary: The penetration behavior of nanoparticles in mucous is influenced by the physicochemical properties of the particles and the mucus microenvironment. In this study, the authors prepared a library of silica nanoparticles with different surface modifications and studied their mucus penetration behavior. They found that particle surface properties, such as PEGylation and amine/carboxyl groups, affected the immobilization and movement of the nanoparticles in mucus. The study provides insights for designing efficient transmucosal nanocarriers for pulmonary diseases.

ACS NANO (2023)

Article Chemistry, Physical

Langmuir-Blodgett transfer from the oil-water interface

Guangle Li, Xiaojie Xu, Yi Y. Zuo

Summary: Recently, the study of Langmuir-Blodgett (LB) films has been primarily focused on self-assembled monolayers at the air-water surface, with limited research on the oil-water interface. This study introduces a new experimental method called constrained drop surfactometry (CDS) for preparing and characterizing LB films from the oil-water interface.


Article Biophysics

Phase transitions of the pulmonary surfactant film at the perfluorocarbon-water interface

Guangle Li, Xiaojie Xu, Yi Y. Zuo

Summary: Pulmonary surfactant is a lipid-protein complex that forms a thin film at the air-water surface of the lungs. The phase behavior of this surfactant film at the PFC-water interface is relatively unknown. This study provides new biophysical insight into the phase transitions of natural pulmonary surfactant films at the PFC-water interface, which has implications for the development of liquid ventilation and liquid breathing techniques.


Article Biophysics

Biophysical function of pulmonary surfactant in liquid ventilation

Guangle Li, Xiaojie Xu, Yi Y. Zuo

Summary: Liquid ventilation is a mechanical ventilation technique that uses oxygen-ated perfluorocarbon (PFC) liquids to fill the lung. It is important to use pulmonary surfactant in addition to PFC, as PFC cannot replace the function of surfactant in reducing interfacial tension and increasing lung compliance. This study explores the adsorption and surface activity of a natural surfactant at the PFC-water interface, revealing its role in regulating interfacial tension during liquid ventilation.


Article Multidisciplinary Sciences

Airborne fine particles drive H1N1 viruses deep into the lower respiratory tract and distant organs

Zheng Dong, Juan Ma, Jiahuang Qiu, Quanzhong Ren, Qinge Shan, Xuefeng Duan, Guangle Li, Yi Y. Zuo, Yu Qi, Yajun Liu, Guoliang Liu, Iseult Lynch, Min Fang, Sijin Liu

Summary: Mounting data suggest that environmental pollution due to airborne fine particles (AFPs) increases the occurrence and severity of respiratory virus infection in humans. However, it is unclear whether and how interactions with AFPs alter viral infection and distribution. Our study reveals synergetic effects between various AFPs and the H1N1 virus, regulated by physicochemical properties of the AFPs. These findings highlight the key role of AFPs in driving viral infection throughout the respiratory tract and beyond, emphasizing the need for stronger air quality management and pollution reduction policies.


Article Physiology

Constrained drop surfactometry for studying adsorbed pulmonary surfactant at physiologically relevant high concentrations

Xiaojie Xu, Guangle Li, Yi Y. Zuo

Summary: A new in vitro biophysical model called constrained drop surfactometry was developed to study the biophysical properties of the pulmonary surfactant film at high concentrations. The experimental results suggest that the multilayers formed act as a buffer zone to store surface-active materials under extreme conditions.


Article Engineering, Environmental

Adverse Biophysical Impact of e-Cigarette Flavors on Pulmonary Surfactant

Ria A. Goros, Xiaojie Xu, Guangle Li, Yi Y. Zuo

Summary: The attractiveness and variety of flavors in e-cigarettes attract young people to use them. However, studies have shown that the flavoring chemicals in e-cigarettes can have adverse effects on the function of pulmonary surfactants. This study used a new method called constrained drop surfactometry to investigate the biophysical impact of flavored e-cigarette aerosols on natural pulmonary surfactants. The results showed that different flavors of e-cigarette aerosols have a flavor-dependent inhibitory effect on the properties of pulmonary surfactants. A qualitative phase diagram was proposed to predict the potential hazards of different flavoring chemicals.


Article Chemistry, Multidisciplinary

pH-Mediated Mucus Penetration of Zwitterionic Polydopamine-Modified Silica Nanoparticles

Yubin Ma, Yiyang Guo, Shan Liu, Yu Hu, Cheng Yang, Gang Cheng, Changying Xue, Yi Y. Zuo, Bingbing Sun

Summary: Zwitterionic polymers with superior antifouling properties are promising trans-mucus nanocarriers. The effect of pH microenvironment on the trans-mucus fate of pH-sensitive zwitterionic polymers is unclear. This study prepared zwitterionic polydopamine-modified silica nanoparticles (SiNPs-PDA) and found that the diffusion of SiNPs-PDA in mucus with a pH value of 5.6 was 3 times faster than in mucus with pH values 3.0 or 7.0. The pH-mediated mucus penetration behavior of SiNPs-PDA was mediated by hydrophobic and electrostatic interactions and hydrogen bonding between mucin and the particles.


Article Ophthalmology

Effect of Model Tear Film Lipid Layer on Water Evaporation

Xiaojie Xu, Guangle Li, Yi Y. Zuo

Summary: The purpose of this research is to develop an in vitro model to study the effect of the tear film lipid layer (TFLL) on water evaporation. An evaporimeter has been invented to study the evaporation resistance of TFLL and the results show that a model TFLL can reduce the water evaporation rate.


Article Engineering, Environmental

Microplastics and Nanoplastics Impair the Biophysical Function of Pulmonary Surfactant by Forming Heteroaggregates at the Alveolar-Capillary Interface

Xiaojie Xu, Ria A. Goros, Zheng Dong, Xin Meng, Guangle Li, Wei Chen, Sijin Liu, Juan Ma, Yi Y. Zuo

Summary: Microplastics are environmental pollutants produced through the degradation of plastic products. Nanoplastics, which are submicrometer debris produced from the fragmentation of microplastics, have been found to have adverse impacts on the biophysical function of pulmonary surfactant. In particular, nanoplastics derived from foam packaging boxes made of polystyrene showed the highest adverse impact. These findings provide insights into the health impact of microplastics and nanoplastics on the respiratory system.


No Data Available