The Role of Ion Electrophoresis in Electroporation-Mediated Molecular Delivery

Electroporation is a widely applied technique to deliver active molecules into the cellular compartment, to perform tasks such as gene therapy and directed stem cell differentiation, among many others. In this technique, an electric field transiently permeabilizes the cellular membrane to facilitate molecular exchange. While the permeabilization process is relatively well understood, the transport mechanisms for molecular delivery are still under debate. In this work, the role of ion electrophoresis in electroporation-mediated molecular delivery is investigated using numerical simulation. The Nernst-Planck equations for ionic transport in the extracellular and intracellular spaces are solved, respectively, and are coupled through a permeabilization model on the membrane. For the latter, an asymptotic Smoluchowski equation system is adopted, following the work of Krassowska and co-authors. The simulation is used to investigate the delivery of calcium ions into Chinese hamster ovary cells. The results indicate that ion electrophoresis is the dominant mode of transport in the delivery of small charged molecules. Furthermore, the achievable intracellular concentration is strongly influenced by the conductivity difference between the cytoplasm and the buffer, a phenomenon known as “field-amplified sample stacking”. The results agree qualitatively with the fluorescence measurements by Gabriel and Teissie´ (1999), and suggest a new possibility to simultaneously improve cell viability and efficiency in electroporation-mediated molecular delivery.