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BMC Biochemistry

, 5:10

First Online: 19 July 2004Received: 01 February 2004Accepted: 19 July 2004

Abstract

BackgroundElectroporation is a common method to introduce foreign molecules into cells, but its molecular basis is poorly understood. Here I investigate the mechanism of pore formation by direct molecular dynamics simulations of phospholipid bilayers of a size of 256 and of more than 2000 lipids as well as simulations of simpler interface systems with applied electric fields of different strengths.

ResultsIn a bilayer of 26 × 29 nm multiple pores form independently with sizes of up to 10 nm on a time scale of nanoseconds with an applied field of 0.5 V-nm. Pore formation is accompanied by curving of the bilayer. In smaller bilayers of ca. 6 × 6 nm, a single pore forms on a nanosecond time scale in lipid bilayers with applied fields of at least 0.4 V-nm, corresponding to transmembrane voltages of ca. 3 V. The presence of 1 M salt does not seem to change the mechanism. In an even simpler system, consisting of a 3 nm thick octane layer, pores also form, despite the fact that there are no charged headgroups and no salt in this system. In all cases pore formation begins with the formation of single-file like water defects penetrating into the bilayer or octane.

ConclusionsThe simulations suggest that pore formation is driven by local electric field gradients at the water-lipid interface. Water molecules move in these field gradients, which increases the probability of water defects penetrating into the bilayer interior. Such water defects cause a further increase in the local electric field, accelerating the process of pore formation. The likelihood of pore formation appears to be increased by local membrane defects involving lipid headgroups. Simulations with and without salt show little difference in the observed pore formation process. The resulting pores are hydrophilic, lined by phospholipid headgroups.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2091-5-10 contains supplementary material, which is available to authorized users.

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Autor: D Peter Tieleman

Fuente: https://link.springer.com/article/10.1186/1471-2091-5-10



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