Fig. 1.

The transient aqueous pore hypothesis. (A) The sequence of lipid rearrangements that lead to a conductive (hydrophilic, or toroidal) pore. Formation proceeds from the unperturbed membrane (i) via a nonconducting hydrophobic pore generated by the parting of lipids but involving no molecular reorientation (ii). At sufficiently large radii, however, lipids rearrange and head groups line the pore lumen (iii). (B) Electropore energy landscape highlighting the hydrophobic and hydrophilic pore free energies (dashed and solid lines, respectively) using the equations and parameter values from ref. 16, which are those commonly used in theoretical electroporation literature. Their intersection is indicated at the asterisk (*); we refer to this energy barrier as E*. The gray line is the hydrophilic pore energy at V_applied = 0 mV; yellow through to red plots the reduction in free energy from 100 to 700 mV. Increasing the applied potential difference is predicted to lower and broaden the local energy minimum that supports the hydrophilic pore, and lower the barrier to unbounded pore expansion.