A molecular dynamic study of cholesterol rich lipid membranes: comparison of electroporation protocols

• MD protocols mimicking the action of both ns and ms electric pulses were used.
• EP threshold increases linearly with chol content for ns pulses.
• EP threshold levels off at a mole ratio of chol to lipid 30:70 for ms pulses.
• For ns pulses pores are hydrophilic.
• For ms pulses pores are hydrophobic.

We report on a molecular dynamics (MD) simulation study of the electroporation of lipid bilayers at different cholesterol contents using protocols mimicking “traditional” electroporation, i.e. low intensity millisecond pulses (msEP), and high intensity nanosecond electric pulses (nsEP). The results show that addition of cholesterol in concentrations of lipid:sterol ranging from 20 to 50 mol% enhances substantially the membrane cohesion, which is manifested by an increase of the electroporation threshold (Uthr). This increase is steady in the case of the nsEP protocol, reaching roughly a factor 2 in the 50 mol% samples. In contrast, for the msEP protocol, Uthr increases by 50% upon addition of 30 mol% cholesterol then levels off. Furthermore, pores formed under msEP are found to possess morphologies much different from the usually reported hydrophilic “electropores” encountered under the nsEP protocol, which may have profound consequences on the transport properties of “electroporated” membranes. Hence, this study reveals that cell membrane models containing the ubiquitous cholesterol component respond quite differently to the two electroporation techniques, in contrast to what has been found for simple zwitterionic bilayers.