How do electric fields open pores in cell membranes?

What is it about?

Electroporation consists in the perforation of holes in the cell membrane by an electric field to allow delivering of therapeutical substance to the cell. A Franco-German team of scientists unveils in the journal PNAS elements essential to the understanding of this widely used but still poorly understood phenomenon.

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Photo by Julian Böck on Unsplash

Photo by Julian Böck on Unsplash

Why is it important?

Electroporation is a well-established technique for overcoming the cell membrane barrier. A brief electrical pulse punctures a pore in the membrane allowing the delivery of therapeutic substances inside the cells: drugs, DNA and many other biomolecules. But this technique, which represents a multi-billion dollar market, rests surprisingly on thin fundamental knowledge. In a paper just published in the journal PNAS, a team from the CNRS and colleagues from the University of Freiburg-im-Breisgau unveil a large set of new data on pore formation in lipid membranes under electric field. These results not only show that existing models of pore formation cannot account for the observations, but also suggest a more likely mechanism of membrane hole formation. Lipid membranes are two-dimensional self-assemblies of amphiphilic molecules. They form the outer and inner walls of cells, organizing cellular compartments, controlling material exchange, and supporting reactions, signal transmission, and many other processes essential to life. These membranes are very efficient flow controllers: if they allow water molecules to easily cross the 5 nm thick lipid barrier, they remain on the other hand very impermeable to the majority of water-soluble molecules. This impermeability is overcome by the application of electric fields, which open up the pores. At the heart of the discrepancies between the existing models and the new experiments published in the journal PNAS is the frequency of pore formation under an electric field. This frequency, which depends on the amount of energy needed to open a pore, is measured by counting how many pores form during one second of electric field application. Under increasing electric fields, this energy is reduced and the pores can open spontaneously. Existing models assume that the electric field applies pressure to the membrane, which facilitates pore opening. But such an effect predicts a quadratic dependence on the field: doubling the value of the field should decrease the energy cost by a factor of four. In contrast, the scientists observed that the lowering of the energy barrier varies linearly with the electric field. This linear dependence suggests a different mode of action of the field: by rotating the molecules of the thin water layer in intimate contact with the membrane, the electric field would destabilize the membrane-water interface.

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