Kinetics, statistics, and energetics of lipid membrane electroporation studied by molecular dynamics simulations.

Böckmann R, De Groot BL, Kakorin S, Neumann E, Grubmueller H (2008)

Publication Status: Published

Publication Type: Journal article, Original article

Publication year: 2008

Journal

Biophysical Journal Biophysical Society

Book Volume: 95

Pages Range: 1837-50

Volume: 95

Issue: 4

Journal Issue: 4

DOI: 10.1529/biophysj.108.129437

Abstract

Membrane electroporation is the method to directly transfer bioactive substances such as drugs and genes into living cells, as well as preceding electrofusion. Although much information on the microscopic mechanism has been obtained both from experiment and simulation, the existence and nature of possible intermediates is still unclear. To elucidate intermediates of electropore formation by direct comparison with measured prepore formation kinetics, we have carried out 49 atomistic electroporation simulations on a palmitoyl-oleoyl-phosphatidylcholine bilayer for electric field strengths between 0.04 and 0.7 V/nm. A statistical theory is developed to facilitate direct comparison of experimental (macroscopic) prepore formation kinetics with the (single event) preporation times derived from the simulations, which also allows us to extract an effective number of lipids involved in each pore formation event. A linear dependency of the activation energy for prepore formation on the applied field is seen, with quantitative agreement between experiment and simulation. The distribution of preporation times suggests a four-state pore formation model. The model involves a first intermediate characterized by a differential tilt of the polar lipid headgroups on both leaflets, and a second intermediate (prepore), where a polar chain across the bilayer is formed by 3-4 lipid headgroups and several water molecules, thereby providing a microscopic explanation for the polarizable volume derived previously from the measured kinetics. An average pore radius of 0.47 +/- 0.15 nm is seen, in favorable agreement with conductance measurements and electrooptical experiments of lipid vesicles.

Authors with CRIS profile

Rainer Böckmann Professur für Computational Biology

Involved external institutions

Max-Planck-Institut für biophysikalische Chemie (Karl-Friedrich-Bonhoeffer-Institut) / Max Planck Institute for Biophysical Chemistry DE Germany (DE) Universität Bielefeld DE Germany (DE)

How to cite

APA:

Böckmann, R., De Groot, B.L., Kakorin, S., Neumann, E., & Grubmueller, H. (2008). Kinetics, statistics, and energetics of lipid membrane electroporation studied by molecular dynamics simulations. Biophysical Journal, 95(4), 1837-50. https://dx.doi.org/10.1529/biophysj.108.129437

MLA:

Böckmann, Rainer, et al. "Kinetics, statistics, and energetics of lipid membrane electroporation studied by molecular dynamics simulations." Biophysical Journal 95.4 (2008): 1837-50.

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