The buckling-condensation mechanism driving gas vesicle collapse

Abstract

Gas vesicles (GVs) are proteinaceous cylindrical shells found within bacteria or archea growing in aqueous environments and are composed primarily of two proteins, gas vesicle protein A and C (GvpA and GvpC). GVs exhibit strong performance as next-generation ultrasound contrast agents due to their gas-filled interior, tunable collapse pressure, stability in vivo and functionalizable exterior. However, the exact mechanism leading to GV collapse remains inconclusive, which leads to difficulty in predicting collapse pressures for different species of GVs and in extending favorable nonlinear response regimes. Here, we propose a two stage mechanism leading to GV loss of echogenicity and rupture under hydrostatic pressure: elastic buckling of the cylindrical shell coupled with condensation driven weakening of the GV membrane. Our goal is to therefore test whether the final fracture of the GV membrane occurs by the interplay of both mechanisms or purely through buckling failure as previously believed. To do so, we (1) compare the theoretical condensation and buckling pressures with that for experimental GV collapse and (2) describe how condensation can lead to plastic buckling failure. GV shell properties that are necessary input to this theoretical description, such as the elastic moduli and wettability of GvpA, are determined using molecular dynamics simulations of a novel structural model of GvpA that better represents the hydrophobic core. For GVs that are not reinforced by GvpC, this analytical framework shows that the experimentally observed pressures resulting in loss of echogenicity coincide with both the elastic buckling and condensation pressure regimes. We also found that the stress strain curve for GvpA wetted on both the interior and exterior exhibits a loss of mechanical stability compared to GvpA only wetted on the exterior by the bulk solution. We identify a pressure vs. vesicle size regime where condensation can occur prior to buckling, which may preclude nonlinear shell buckling responses in contrast imaging.