Hydrostatic Pressurization of Lung Surfactant Microbubbles: Observation of a Strain-Rate Dependent Elasticity

Abstract

The microbubble offers a unique platform to study lung surfactant mechanics at physiologically relevant geometry and length scale. In this study, we compared the response of microbubbles (∼15 μm initial radius) coated with pure dipalmitoyl-phosphatidylcholine (DPPC) versus naturally derived lung surfactant (SURVANTA) when subjected to linearly increasing hydrostatic pressure at different rates (0.5-2.3 kPa/s) at room temperature. The microbubbles contained perfluorobutane gas and were submerged in buffered saline saturated with perfluorobutane at atmospheric pressure. Bright-field microscopy showed that DPPC microbubbles compressed spherically and smoothly, whereas SURVANTA microbubbles exhibited wrinkling and smoothing cycles associated with buckling and collapse. Seismograph analysis showed that the SURVANTA collapse amplitude was constant, but the collapse rate increased with the pressurization rate. An analysis of the pressure-volume curves indicated that the dilatational elasticity increased during compression for both shell types. The initial dilatational elasticity for SURVANTA was nearly twice that of DPPC at higher pressurization rates (>1.5 kPa/s), producing a pressure drop of up to 60 kPa across the film prior to condensation of the perfluorobutane core. The strain-rate dependent stiffening of SURVANTA shells likely arises from their composition and microstructure, which provide enhanced in-plane monolayer rigidity and lateral repulsion from surface-associated collapse structures. Overall, these results provide new insights into lung surfactant mechanics and collapse behavior during compression.

High-precision acoustic measurements of the nonlinear dilatational elasticity of phospholipid coated monodisperse microbubbles

“…The length of the PEG chain, the length of the primary lipid molecules, temperature, microbubble production method, resting time after synthesis, and phase behavior and microstructure formation of the lipids in the coating may all play a role. [59][60][61] Furthermore, acoustically driven selective loss of shell components may influence shell stiffness. In our previous work, it was shown that the shell elasticity of monodisperse microbubbles formed by flow-focusing and coated by a very similar lipid mixture (DPPC:DPPA:DPPE-PEG5k, 8:1:1 molar ratio) can increase from 0.8 N/m to 2.5 N/m during multiple acoustic insonations 28 which, in part, can now be explained from a slight (2%) decrease in bubble radius due to acoustically driven dissolution.…”

Contrast-enhanced sonography with biomimetic lung surfactant nanodrops

“…Control microbubbles were made with the pure lipid component 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) (Avanti Polar Lipids, Alabaster, AL), as previously described [15]. DPPC was weighed and dissolved in chloroform (Sigma-Aldrich, St. Louis, MO).…”

“…Beractant has been shown to stabilize microbubbles by forming a monolayer at the gas/water interface with attached bilayer folds that extend into the aqueous phase [14]. The Beractant film is transported from the monolayer to the bilayer folds during hydrostatic compression of the microbubble [15]. These attached bilayer folds may serve as a film reservoir for the expanding interface.…”

Reverse engineering the ultrasound contrast agent

“…While these forces ultimately ensure complete bubble dissolution, the rate is hindered by the limited permeability [59] and elasticity [60] of the shell, thereby allowing sufficient stability for an imaging exam. Coated microbubbles dissolve according to a modified Epstein-Plesset relation [61]: dRdt=−H[1−F+Λ/Rρ∞1+2Λ/3Rρ∞][1Ωw+Ωshell] Λ=2MBT(γ0+Eβ)…”

“…a) Uncoated microbubbles containing various gases in a saturated medium dissolving due to surface tension; gas parameters taken from [60]. B) Lipid-coated vs. uncoated air bubbles dissolving in an undersaturated medium ( F = 0.8); lipid shell permeability is taken from [64] and elasticity is taken from [61].…”