Lung Surfactant Adsorption and Inhibition

Inhibition, the impediment of lung surfactant adsorption from the alveolar fluid to the air-water interface, prevents the low surface tensions necessary for proper lung function. This is an important effect in diseases associated with a lack of lung surfactant including neonatal respiratory distress syndrome (NRDS), often due to premature delivery, and acute respiratory distress syndrome (ARDS). The common features of inhibitors are (1) they are not normally present in the alveolar fluid; (2) they are water soluble, and (3) they are surface active.

We have measured adsorption rates of a common soluble inhibitor (albumin) and the commercial lung surfactant Survanta as a function of surface pressure using a recently described technique, quantitative Brewster angle microscopy (BAM), and shown that this behavior is consistent with our theoretical model for adsorption. Small albumin molecules adsorb faster to an interface than the larger surfactant aggregates at low surface pressures; hence the surfactant has to displace inhibitor from the interface in order to adsorb. This leads to an energy barrier to surfactant adsorption, and hence, less surfactant at the interface. As a result, the interface must be compressed further to reach the low surface tensions necessary for lung function. Adding hydrophilic polymers to the surfactant solution has recently been shown in animal models to reverse inhibition; however, the mechanism and method of determining the optimal polymer concentration, molecular weight and chemistry is still unknown. We have proposed that the inhibition reversal is due to the ?depletion effect?, caused by the increase in free volume of the solution when the surfactant is forced to the interface, which increases the polymer entropy. The depletion force helps overcome the barrier to surfactant adsorption and our theory makes specific predictions regarding polymer molecular weight, chemistry and molecular weight which will be tested under this proposal.