Lipid monolayer dilatational mechanics during microbubble gas exchange

Lipid-coated microbubbles are being developed for a variety of biomedical applications in imaging and therapy. In order to better understand microbubble stability and in vivo fate, it is important to elucidate the mechanical properties of the phospholipid monolayer shell. Here, a gas exchange method was used to probe the monolayer dilatational properties of individual microbubbles. The microbubbles were observed to grow and then dissolve back to the initial diameter in a manner that depended on both microbubble size and lipid composition. The experimental diameter–time curves were analyzed with a gas transport model employing the energy barrier theory for monolayer permeation to account for gas species, acyl-chain length and variable surface pressure. Model analysis allowed computation of apparent surface tension as a function of area, which exhibited a characteristic “flag-shaped” curve comprising three regimes: (i) linear elastic expansion, (ii) nonlinear relaxation during expansion and (iii) linear elastic compression. A comparison of fitted model parameters suggested a molecular mechanism involving expansion, rupture and lipid lateral diffusion in the monolayer shell during growth and lipid domain growth and packing during dissolution. Overall, these results provide new physical insights into lipid monolayer behavior that are relevant to understanding microbubble stability and medical performance.