Lung/pulmonary surfactant is a phospholipid-protein complex that lines a thin film at the air-water interface of the lung. The surfactant film of the lung plays a dual role of surface tension reduction and host defense against inhaled pathogens and particles. By reducing alveolar surface tension, lung surfactant stabilizes alveoli against collapse and maintains a large surface area of the lung for gas exchange.

Synthesis, transformation, and turnover of lung surfactant (cartoon adapted from Whitsett and Weaver. 2002. N. Eng. J. Med. 347:2141). The EM pictures show the morphological transformation of lung surfactant (adapted from Goerke. 1998. BBA 1408:79) and the multilaminar structure (MS) of surfactant film at the air-water interface of alveoli (adapted from Schürch et al. 1998. BBA 1408:180).

Deficiency of lung surfactant in premature newborns causes respiratory distress syndrome (RDS), a leading cause of perinatal mortality. Supplementing exogenous surfactants extracted from animals' lung to preemies suffering from RDS has completely altered neonatal care in industrialized countries. Surfactant therapy has also been applied to the acute respiratory distress syndrome (ARDS) but to date with only limited success, which might be in part due to surfactant inhibition.

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.

The study of lung surfactant is highly interdisciplinary. It covers a broad range of research areas, from pure scientific investigation to more engineering orientated studies, from traditional physiological and biochemical research to emerging areas involving nanotechnology, from fundamental colloid and surface science to clinical research in neonatology and pulmonology.

Interdisciplinary study of lung surfactant.

Research in our lab focuses on the biophysical study of lung surfactant from both macroscopic and microscopic points of view. On the one hand, we study surface tension of lung surfactant using advanced surface tensiometry. On the other hand, we probe direct molecular interactions between phospholipids and proteins at the interface using atomic force microscopy (AFM). This multidisciplinary approach allows us to explore the biophysical properties of lung surfactant in detail. The ultimate goal of this research is to translate the fundamental study to biomedical and clinical practice of lung surfactant in treating infant and adult respiratory diseases. It should be noted that the approach we developed in studying lung surfactant films is also applicable to the study of other biomembranes and self-assembled monolayers, bilayers, and multilayers.

Surface tension vs. surface area isotherms for dynamic cycling of lung surfactant at physiological relevant conditions. The measurement was conducted using a captive bubble surfactometer (CBS) at 37 ºC. The rate of compression is 5 sec/cycle to mimic breathing. The compression ratio is much higher than that in the lung, in order to study film collapse. It is noted that lung surfactant film can decrease surface tension down to near-zero with about 20% area reduction (at which the film collapses); while maintains a surface tension around 30 mN/m upon film expansion (at which surfactant readsorbs/respreads back to the interface). This measurement confirms surface tension in the lung likely ranges from ~0 to ~30 mN/m, and only exhibits limited hysteresis (i.e., limited energy loss) when the compression ratio is less than 20%. The figure is adapted from Neumann et al. (eds) Applied Surface Thermodynamics 2nd ed., Chapter 5, Taylor&Francis, 2010.

AFM structures of bovine lipid extract surfactant (BLES) films at room temperature. Upon compression, BLES monolayers exhibit continuously phase transitions from a fluid-like liquid-expanded (LE) phase to a solid-like tilted-condensed (TC) phase. AFM detected the phase transition occurs on both micrometer scale and nanometer scale. (The insert at surface pressure 30 mN/m has a scanning area of 1x1 µm.) Upon monolayer compression to 40 mN/m, most microdomains break into nanodomains. Between 40 and 50 mN/m, BLES monolayers undergo a monolayer-to-multilayer transition plateau. Beyond this plateau, the interfacial monolayer is transformed into multilayers by localized film collapse. The collapsed multilayer structure is closely attached to the interfacial monolayer, and respread to interface during the subsequent film expansion. The figure is adapted from Zuo et al. 2008. Biophys. J. 94:3549.

This AFM image (scan size 5um x 5 um) shows the micro- and nano- structures of a commercial surfactant preparation derived from calves' lungs (Infasurf®). It shows phospholipid phase separation in a single moon-shaped domain that consists of a high tilted-condensed phase (~1 nm), an intermediately-high liquid-ordered phase (~0.8 nm), and a low liquid-expanded phase. This rich phase behavior revealed by AFM in surfactant monolayers appears to relate to cholesterol content in this preparation. Appears in December of the Bruker Atomic Force Microscopy 2011 Calendar. Image courtesy of Hong Zhang, Yi Wang, and Yi Zuo, University of Hawaii at Manoa. Also see Hong et al. 2011 Biochim. Biophys. Acta 1808: 1832.