A shock to the system

Eisenstein, Michael

doi:10.1038/nmeth0106-66

Classic Protocol
Published: January 2006

A shock to the system

Michael Eisenstein

Nature Methods volume 3, page 66 (2006)Cite this article

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Since the days of Benjamin Franklin, scientists have been keenly aware of the dangerous (and painful) potential of a strong electric current; likewise, at a smaller scale, scientists have been aware for some time that a strong electric pulse can kill cells by inducing membrane lysis. However, some researchers in the 1970s were surprised to find that for pulses of milder strength, cells seem to follow the principle of 'whatever doesn't kill you only makes you stronger'—or at least bigger. Indeed, a landmark study by Kinosita and Tsong demonstrated that the application of electrical pulses could be used to induce the formation of transient, reversible openings in the plasma membranes of human erythrocytes, triggering cell expansion as a result of the uptake of a variety of ions and organic compounds from the surrounding medium¹.

Another pioneer in the field, Eberhard Neumann of the Max-Planck-Institut in Munich, had also spent several years characterizing this phenomenon in a variety of mammalian cell types. Building on his own work, as well as that of fellow German cell biologist Ulrich Zimmermann, Neumann ultimately arrived at the idea of using this process as a method for delivering DNA into mammalian cells. Using moderate voltages, Neumann was readily capable of coaxing mouse fibroblasts into taking up and stably expressing plasmid-based foreign genes, with an efficiency that rivaled existing techniques for transfection, such as calcium phosphate and liposomes². In a subsequent paper, Neumann's group investigated the mechanics of this process, which they now dubbed 'electroporation', theorizing that interactions of the lipid membrane with the external electric field led to shifts of certain lipid head groups into more favorable dipole configurations—shifts that result in the thinning and eventual perforation of certain portions of the plasma membrane³. Surprisingly, the picture has not grown especially clearer in the subsequent quarter of a century, and the actual mechanics behind this electrically induced membrane pore formation remain vague and controversial, particularly with regard to the highly temporary nature of the resulting openings⁴.

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