Shock Wave-Induced Damage and Poration in Eukaryotic Cell Membranes

Abstract

Shock waves are known to permeabilize eukaryotic cell membranes, which may be a powerful tool for a variety of drug delivery applications. However, the mechanisms involved in shock wave-mediated membrane permeabilization are still poorly understood. In this study, the effects on both the permeability and the ultrastructural features of two human cell lineages were investigated after the application of underwater shock waves in vitro. Scanning Electron Microscopy of cells derived from a human embryo kidney (HEK)-293 and Michigan Cancer Foundation (MCF)-7 cells, an immortalized culture derived from human breast adenocarcinoma, showed a small amount of microvilli (as compared to control cells), the presence of hole-like structures, and a decrease in cell size after shock wave exposure. Interestingly, these effects were accompanied by the permeabilization of acid and macromolecular dyes and gene transfection. Trypan blue exclusion assays indicated that cell membranes were porated during shock wave treatment but resealed after a few seconds. Deformations of the cell membrane lasted for at least 5 min, allowing their observation in fixed cells. For each cell line, different shock wave parameters were needed to achieve cell membrane poration. This difference was correlated to successful gene transfection by shock waves. Our results demonstrate, for the first time, that shock waves induce transient micro- and submicrosized deformations at the cell membrane, leading to cell transfection and cell survival. They also indicate that ultrastructural analyses of cell surfaces may constitute a useful way to match the use of shock waves to different cells and settings.

Sonoporation based on repeated vaporization of gold nanodroplets

“…The possible reason for increased cell death may be due to failed resealing of pores on the cell membrane. It was found that after cells were sonoporated, the generated pores on the cell membrane would be resealed after a few to few tens of seconds for survival 36,38 . In our case, the PRF was 20 Hz so the time for completing 5000 activation firings was 250 s, thus failing to reseal might be possible because the vaporization and inertial cavitation kept generating pores or enlarging pores during this period of time.…”

“…With the aim of reducing driving energy and the consumption of AuNDs, in this study, we made an effort to leverage the repeatability of the vaporization/recondensation cycle to achieve effective sonoporation. Increasing activation firings can enhance both inertial cavitation and sonoporation 35–37 . However, we found that as more activation numbers were given, lower vaporization and inertial cavitation effects were observed (Figure 5).…”

“…Increasing acti- vation firings can enhance both inertial cavitation and sonoporation. [35][36][37] However, we found that as more activation numbers were given, lower vaporization and inertial cavitation effects were observed (Figure 5). This suggests that additional activation firings result in the destruction of AuNDs.…”

Effect of low‐energy shock wave therapy on intravesical epirubicin delivery in a rat model of bladder cancer

“…Fluorescence spectrophotometric analysis of EPI in the bladder tissues of the EPI plus LESW group revealed that LESW significantly increased urothelial permeability and absorption of intravesical EPI. This could be explained by an LESW‐induced shearing force which resulted in transient deformations at the cell membranes, so cell size decreased, hole‐like structures were developed and the cell membranes became temporarily porated [28]. Similarly, Chuang et al [12] reported increased urothelial permeability documented by the significant downregulation of E‐cadherin and zonula occludens‐1 (tight junction molecular markers), facilitated drug delivery and inhibited bladder hyperactivity after combined LESW application and intravesical botulinum toxin A instillation in rats.…”

Radial extracorporeal shock wave promotes the enhanced permeability and retention effect to reinforce cancer nanothermotherapeutics

“…Under this setting, rESWT-induced endothelial leakiness should supposedly favor the delivery and extravasation of nano-drugs into the tumor microenvironment and thereby reinforce tumor targeting and the following treatment. In fact, recent burgeoning evidence indicates that extracorporeal shock wave (ESW) is applicable to treat tumors, due to increased plasma membrane permeability and intracellular drug concentration that are ascribed to ESW-driven cavitation [21][22][23]. Thus, it would be of proven importance to extend ESW applications in cancer therapeutics, although a wider caliber of combinatory therapies and deeper understanding of molecular mechanisms are warranted.…”