Using computer simulations to study biological problems
As computers have become more powerful and software more efficient, molecular dynamics simulations have rapidly grown in size and complexity. This is setting the stage for new discoveries as it enables researchers like Svetlana Baoukina to examine simulations at a level of scope and complexity once thought impossible. This has also helped illustrate challenges in current analysis. For example, one of Baoukina’s recent research projects was inspired by questions related to the function of lung surfactant.
Lung surfactant is a monomolecular film that covers the interface of the alveoli and air. The alveoli are small structures in the lung where gas exchange takes place. During the breathing cycle, the area of this interface changes substantially. Upon inhalation the alveoli expand, increasing the area of the interface, while during exhalation the opposite occurs. At most interfaces, for instance the air/water interface, changing the area requires a significant amount of work, expressed quantitatively by the surface tension at the interface. The main role of lung surfactant is to reduce the surface tension, so that breathing does not require significant work.
For Baoukina’s project, she used simulations of biological membranes and monolayers to mimic lung surfactant and illustrate the large-scale transformation and complex mixtures of lipids and proteins that occurs during the gas exchange process. She used a simulation of a monolayer with three phospholipid components, cholesterol, lung surfactant protein, water, and ions on a ten microsecond time scale. In her simulation, phase separation occured followed by formation of a bilayer fold in which lipids and lung surfactant protein formed a highly curved structure in the aqueous phase. She also used Voronoi analysis to obtain detailed physical properties of the different components and phases, and calculate local mean and Gaussian curvatures of the bilayer fold.
Results from this research have the potential to contribute to the diagnosis and treatment of respiratory disorders caused by surfactant dysfunction or inactivation, such as forms of respiratory distress syndrome or asthma.