Microbubble-Enhanced Cell Membrane Permeability in High Gravity Field

Abstract

Cell permeability controls the transportation of extracellular materials through cell membranes, which plays a critical role in drug and gene delivery. This work reports an innovative method to enhance the cell permeability through cell-bubble interactions in a high gravity field. In the presence of microbubbles, the cell membrane permeability of mammalian cells was significantly increased in the high gravity field, and up to 80% THP-1 and 70% MCF-7 cells were permeabilized by using FITC-Dextran with average molecular weight of 40 and 70 kDa as fluorescent markers which were found to locate in both cytoplasm and cell nucleus by using a confocal microscope. Micro-scale pores were detected on the cell membrane by a scanning electron microscope after the cell-microbubble interactions in the high gravity field. The delivery efficiency of FITC-Dextran could be further enhanced in gravity field of higher strength and in solutions with higher volume fraction of microbubbles, though the cell viability would also fall under extreme conditions. A simplified model was proposed to compare the contributions of surface forces (i.e., Derjaguin–Landau–Verwey–Overbeek (DLVO) interaction force and membrane undulation force) with hydrodynamic force associated with cell-bubble interactions in the high gravity field. The hydrodynamic force was found to dominate the cell-bubble interaction while the DLVO force and membrane undulation force only play an important role at small separation (<10 nm) and low relative velocity of approach (i.e., low gravity field strength). The enhanced cell membrane permeability and formation of micro-scale pores are mainly due to the microbubble-cell interactions through collision and/or cavitation effects from the bursting of microbubbles. Our results have important implications in many bioengineering processes which are dependent on cell membrane permeability.