Pulmonary surfactant

Pulmonary surfactant is a complex mixture of phospholipids and proteins that forms a thin film at the air–water interface of the lung alveoli. This surfactant film plays dual physiological roles in reducing surface tension and providing host defense against inhaled pathogens and particulate matter. By lowering alveolar surface tension, pulmonary surfactant stabilizes alveoli against collapse during respiration and preserves the large surface area required for efficient gas exchange.

Deficiency of pulmonary surfactant in premature newborns causes neonatal respiratory distress syndrome (RDS), a major cause of perinatal morbidity and mortality. The development of exogenous surfactant replacement therapy using surfactants extracted from animal lungs has revolutionized neonatal intensive care and dramatically improved the survival of premature infants with RDS. Surfactant therapy has also been explored for the treatment of acute respiratory distress syndrome (ARDS) in both children and adults. However, clinical outcomes for ARDS have thus far shown only limited success, which may be attributable, at least in part, to surfactant inhibition by plasma proteins, inflammatory mediators, and inhaled toxic substances.

Research in our laboratory focuses on the multiscale biophysical study of pulmonary surfactant from both macroscopic and microscopic perspectives. At the macroscopic level, we investigate the surface activity of pulmonary surfactant using constrained drop surfactometry (CDS), a droplet-based tensiometric technique developed in our laboratory. At the microscopic level, we probe the molecular interactions between phospholipids and proteins at interfaces using atomic force microscopy (AFM) and molecular dynamics (MD) simulations. This multidisciplinary and multiscale approach enables detailed characterization of the biophysical properties and molecular mechanisms of pulmonary surfactant. The ultimate goal of our research is to translate these fundamental insights into biomedical and clinical applications of pulmonary surfactant for the prevention and treatment of infant and adult respiratory diseases. 

Molecular dynamics (MD) is a computational simulation method that models the physical motions and interactions of atoms and molecules by numerically solving Newton’s equations of motion. Using molecular mechanics force fields, a predefined number of molecules—ranging from hundreds to millions—are allowed to interact within a computer-simulated virtual environment with specified initial positions and velocities. The system then evolves over time toward thermodynamic equilibrium. By analyzing the resulting molecular configurations and trajectories using statistical mechanical theories, thermodynamic and kinetic properties of the system can be determined.

We have applied MD simulations extensively to the study of pulmonary surfactant biophysics, particularly to investigate the molecular interactions among surfactant lipids, proteins, and inhaled substances at biologically relevant interfaces. Combined with experimental techniques, MD simulations provide molecular-level insights into the structure, dynamics, and functional mechanisms of pulmonary surfactant films.