Polymer Depletion Forces and Surfactant Adsorption

Introduction Lung surfactant is a mixture of lipids, primarily dipalmitoylphosphatidylcholine, and several specific proteins, that lines the interior of the lung alveoli. Lung surfactant lowers the interfacial tension in the lungs, thereby insuring a negligible work of breathing and uniform lung inflation. The absence of lung surfactant in premature infants leads to neonatal Respiratory Distress Syndrome, which can be treated by delivering replacement surfactants, often derived from animals, to the lungs. Such surfactants often provide immediate relief from symptoms and improved oxygenation and gas exchange. However, in some infants and adults, the presence of blood serum proteins or other surface-active species not normally present in the alveolar space may inhibit lung surfactant performance and may play a major role in the development of Acute Respiratory Distress Syndrome (ARDS) [1]. ARDS is often fatal and there is no known treatment. We have found that adding ionic or non-ionic polymers to mixtures of organic extracts of surfactants enhance surface activity and reduce inactivation in vitro and in vivo [2]. The origin of this inhibition reversal is likely the enhanced adsorption of surfactant due to the polymer induced depletion force [3,4]. In this work, a theoretical description of the depletion force on surfactant adsorption is presented and predictions are made to suggest how to optimize surfactant/polymer mixtures for treatments of ARDS. Origin of Inhibition by Soluble, Surface-Active Substances Inhibition is known to be strongly dependent on both the species and concentration of inhibitor [1]. In Figure 1, surface pressures of fibrinogen, albumin and IgG, three proteins commonly implicated in surfactant inhibition, are given as a function of concentration. The surface pressure exerted by a surface active, soluble protein (or any other species) is typically a logarithmic function of concentration up to a certain bulk concentration at which the surface becomes saturated. From Fig. 1, albumin and fibrinogen concentrations .1 mg/ml and greater exert surface pressures of about 20 mN/m, while IgG requires 100 times that concentration to reach the same level. Thus, albumin and fibrinogen should not inhibit below .1 mg/ml and IgG should have little effect until 1mg/ml. This prediction agrees well with experiments [5] establishing the relative inhibitory capacity of serum proteins.