Seminars People Information Computing Research
Project III: Interactions Between Pulmonary Mechanical Behavior and Surfactant Molecular Dynamics
P.I.s: Gaver (Biomedical Engineering), Lacks (Chemical Engineering)

This figure represents the multiple scale interactions that occur in the pulmonary system. The entire lung (top left) is comprised of many small-scale structures such as the alveoli (top right). The mechanical properties of the alveoli are determined by the surfactant uptake to the air-liquid interface, a molecular-level response (bottom). This, in turn, influences the overall mechanical behavior of the organ (center). The center figure shows that without surfactant, the entire lung is much less compliant. This has many implications for the overall stability and viability of the organ, and is related to frequently fatal diseases such as infant and acute respiratory distress syndrome. - Donald P. Gaver
At birth, pulmonary airways are liquid-filled and must be inflated from a collapsed state to initiate gas exchange. For healthy infants, a modest inspiratory effort introduces air into the bronchial tree so that the atmosphere can directly communicate with alveoli, the primary site of gas- exchange with blood. Gestationally mature lungs release surfactant from alveolar type II pneumocytes into the lining fluid. Surfactant reduces the air- liquid surface tension and thus decreases the effort necessary to inflate the lung. However, premature infants may lack the ability to produce adequate surfactant, increasing the surface tension. Surfactant insufficiency coupled with the extremely small size of the lung results in an extraordinarily large inspiratory effort necessary to inflate the premature lung, leading to airway atelectasis (extensive collapse of portions of the lung), deranged pulmonary mechanical responses, poor ventilation/perfusion relationships and insufficient alveolar ventilation. These premature airways can be opened by the application of high pressure using a mechanical ventilator, however this damages the epithelial cells that line the airway walls, resulting in respiratory distress syndrome (RDS). Surfactant replacement therapy (SRT), first successfully implemented the late 1980's, has dramatically reduced the number of fatalities associated with this disease. Nevertheless, RDS remains the fourth leading cause of death of premature infants in the United States.
Recent experiments indicate that during compression of an interface the pulmonary surfactant can fold into a multilayer. This multilayer occurs at high primary layer surface concentrations, and results in meta-stability of sub-equilibrium surface tensions. These observations are corroborated by observances using atomic force microscopy (AFM) that show that if surfactant proteins (SP-B and SP-C) are included, a "folding transition" can occur that reduces surface tension and provides a reservoir for surfactant to the interface upon expansion. This response does not occur if SP-B or SP-C are non- existent. We thus hypothesize that these proteins provide an advantageous energy landscape for the production of multi-layers, which are instrumental in creating meta-stable low dynamic surface tensions. We will investigate molecular transport mechanisms, and their effect on surfactant transport in the lung. These models will relate to surfactant spreading, airway reopening and closure. This project will couple molecular dynamics simulations of surfactant/protein adsorption (molecular) to the surface energy that drives fluid flow (macroscale). The goal of our project will be to use fluid mechanical principles coupled to molecular dynamics simulations to determine the interrelationships between surfactant molecular processes and pulmonary lining fluid flow. This will be useful in explaining the importance of surfactant proteins B-C on adsorption characteristics that are critical to proper lung function, and will allow us to simulate ventilation scenarios in surfactant deficient lungs and determine methods for reducing micromechanical stresses that may damage pulmonary tissue.
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Tulane Tulane University
201 Lindy Boggs Center
Computational Science
6823 St. Charles Ave.
New Orleans, LA 70118
(504)862-8391 ccs@tulane.edu