Biomechanics of liquid-epithelium interactions in pulmonary airways

Abstract

The delicate structure of the lung epithelium makes it susceptible to surface tension induced injury. For example, the cyclic reopening of collapsed and/or fluid-filled airways during the ventilation of injured lungs generates hydrodynamic forces that further damage the epithelium and exacerbate lung injury. The interactions responsible for epithelial injury during airway reopening are fundamentally multiscale, since air-liquid interfacial dynamics affect global lung mechanics, while surface tension forces operate at the molecular and cellular scales. This article will review the current state-of-knowledge regarding the effect of surface tension forces on (a) the mechanics of airway reopening and (b) epithelial cell injury. Due to the complex nature of the liquid-epithelium system, a combination of computational and experimental techniques are being used to elucidate the mechanisms of surface-tension induced lung injury. Continued research is leading to an integrated understanding of the biomechanical and biological interactions responsible for cellular injury during airway reopening. This information may lead to novel therapies that minimize ventilation induced lung injury.

Figure 1

Schematic diagram of pressure-volume loops in saline-filled, normal air-filled and injured lungs (ARDS)

Figure 2

AB: Schematic diagrams of airway reopening in a non-collapsed fluid-filled airway (A) and a collapsed airway (B). In both cases, microbubble flows exert complex fluid mechanical forces on the airway wall. These forces, shown schematically as arrows, include normal pressure and tangential shear stresses as well as temporal and spatial gradients in these stresses. Hypothetical cell deformations due to these stresses at different locations are shown schematically in the circular inserts.

Figure 3

Effect of capillary number (Ca) on A: interfacial geometry; B: the shear stress (τ_s), and C: pressure (P) (from Bilek et al. (2003)). H is the channel half-height.

Figure 4

Flow field and surfactant distribution surrounding a semi-infinite finger of air as it steadily propagates through a liquid-filled channel or tube (dashed lines with arrowheads represent fluid streamlines). Surfactant molecules convect with the flow, and develop a non-uniform distribution on the air-liquid interface. Surface-tension gradients on the air-liquid interface can retard the flow through Marangoni stresses (τ_M) that rigidify the interface.

Figure 5

A: Schematic of an air-liquid interface propagating between two flat plates at velocity U with a uniform contact line on the top/bottom wall. B: Pressure field near the interface for zero and nonzero capillary number (Ca). The spatial gradient in pressure, dP/dx, increases with decreasing Ca. C: Spatial gradients in pressure result in a fore-aft pressure difference across the epithelial cells and this pressure difference is hypothesized to rupture the membrane and lead to necrosis.

Figure 6

Correlations of cell necrosis measured using in-vitro experimental models of airway reopening with computational predictions of the maximum A) pressure gradient, B) shear stress and C) shear stress gradient that develop during reopening (from Yalcin et al. (2007)). Data is demarcated by the different channel half-heights (H) and bubble velocities (U) used in the experiments.

Figure 7

Immunoflourescent staining of NF-kB in alveolar epithelial cells exposed to quiescent conditions and 5 dyne/cm² shear flow for 30 minutes. Nuclear translocation of NF-kB indicates that epithelial cells respond to shear stress by up-regulating inflammatory pathways.