The biophysical function of pulmonary surfactant

Abstract

The type II pneumocytes of the lungs secrete a mixture of lipids and proteins that together acts as a surfactant. The material forms a thin film on the surface of the liquid layer that lines the alveolar air sacks. When compressed by the decreasing alveolar surface area during exhalation, the films reduce surface tension to exceptionally low levels. Pulmonary surfactant is essential for preserving the integrity of the barrier between alveolar air and capillary blood during normal breathing. This review focuses on the major biophysical processes by which endogenous pulmonary surfactant achieves its function and the mechanisms involved in those processes. Vesicles of pulmonary surfactant adsorb rapidly from the alveolar liquid to form the interfacial film. Interfacial insertion, which requires the hydrophobic surfactant protein SP-B, proceeds by a process analogous to the fusion of two vesicles. When compressed, the adsorbed film desorbs slowly. Constituents remain at the surface at high interfacial concentrations that reduce surface tensions well below equilibrium levels. We review the models proposed to explain how pulmonary surfactant achieves both the rapid adsorption and slow desorption characteristic of a functional film.

Figure 1

Dependence of pulmonary mechanics on the fluid instilled. Fully deaerated excised feline lungs at ambient temperatures were slowly inflated with either air or saline to the airway-pressures indicated, and then deflated (8). The horizontal dashed line indicates the effect of surface tension on the pulmonary mechanics of fully inflated lungs.

Figure 2

Hypothetical model for the adsorption by phospholipid vesicles to an air-water interface. Adsorption occurs by the following sequential stages: diffusion to the interface; attachment to the surface; insertion of constituents into the interface by a process involving a stalk connecting the vesicle with the surface; and subsequent spreading across the interface. The two principal radii of curvature, R₁ and R₂, for the stalk determine the principal curvatures (c) according to c ≡ 1/R. The two curvatures have opposite signs, c₁ < 0 and c₂ > 0. The dark “Void” would be unfilled by phospholipid leaflets with a constant thickness. Modified from (50,52).

Figure 3

Effect of the hydrophobic surfactant proteins on adsorption of the surfactant lipids (52). Curves give the surface tensions achieved at times following the injection of samples into the subphase below an air/water interface. Calf lung surfactant extract (CLSE) contains the complete set of hydrophobic constituents in pulmonary surfactant obtained from calves. Nonpolar and phospholipids (N&PL) contains the full complement of surfactant lipids, obtained by removing the proteins from CLSE. Concentrations refer to phospholipids. To see this figure in color, go online.

Figure 4

Relevant phospholipid polymorphisms. A. Inverse hexagonal (H_II) phase. Cylindrical monolayers contain an aqueous core and stack into a hexagonal array. B. Bicontinuous cubic (Q_II) phase. Continuous bilayers of phospholipids separate two aqueous compartments. The bilayers at all points have Gaussian curvature. The midpoint of the bilayer follows a periodic minimal surface, at which the two principal curvatures are equal in magnitude and opposite in sign, so that the surface lacks net curvature. The illustrated structure has the primitive surface of the Im$\overline{3}$m space group. Phospholipids form structures with three of the 17 known periodic minimal surfaces (103). To see this figure in color, go online.

Figure 5

Phase behavior of compressed phospholipid monolayers. Films were produced by spreading solutions in immiscible, volatile solvents on the surface of captive bubbles. 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC) forms a disordered monolayer. During slow compression (1.1 h⁻¹) at ambient temperatures (red curve), constituents collapse from the interface at the equilibrium spreading tension (γ_e), and surface tension falls no further. Initially disordered films of dipalmitoyl phosphatidylcholine (DPPC) undergo a phase transition to a condensed phase that resists collapse (black) and readily reduces surface tension to alveolar levels. POPC also reaches low surface tension if compressed faster than the films can collapse (green). At sufficiently low surface tensions, the films transform. They become resistant to collapse and undergo slow cyclic expansion to the γ_e (blue) and recompression (magenta) without evidence of collapse. Modified from (104). To see this figure in color, go online.

Figure 6

Mechanisms of collapse. Compressed phospholipid monolayers may collapse either by flowing at the equilibrium spreading pressure into stacks of the bulk smectic phase adjacent to the interface or by buckling from the interface at lower surface tensions to form bilayers that extend great distances into the subphase. Modified from (105). To see this figure in color, go online.

Figure 7

Coexisting phases in monolayers of extracted calf surfactant. Micrographs depict monolayers of calf lung surfactant extract (CLSE) compressed to a surface pressure of 30 mN/m at ambient temperatures. A. Fluorescence microscopy (from (44)). B. Atomic force microscopy (from (106)). To see this figure in color, go online.