Cell-cycle-dependences of membrane permeability and viability observed for HeLa cells undergoing multi-bubble-cell interactions.

Microbubble-mediated sonoporation is a promising strategy for intracellular gene/drug delivery, but the biophysical mechanisms involved in the interactions between microbubbles and cells are not well understood. Here, HeLa cells were synchronized in individual cycle phases, then the cell-cycle-dependences of the membrane permeability and viability of HeLa cells undergoing multi-bubble sonoporation were evaluated using focused ultrasound exposure apparatus coupled passive cavitation detection system. The results indicated that: (1) the microbubble cavitation activity should be independent on cell cycle phases; (2) G-phase cells with the largest Young's modulus were the most robust against microbubble-mediated sonoporation; (3) G/M-phase cells exhibited the greatest accumulated FITC uptake with the lowest viability, which should be mainly attributed to the chemical effect of synchronization drugs; and (4) more important, S-phase cells with the lowest stiffness seemed to be the most susceptible to the mechanical effect generated by microbubble cavitation activity, which resulted in the greatest enhancement in sonoporation-facilitated membrane permeabilization without further scarifying their viability. The current findings may benefit ongoing efforts aiming to pursue rational utilization of microbubble-mediated sonoporation in cell-cycle-targeted gene/drug delivery for cancer therapy.