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Biophysical Journal 85:1611-1623 (2003)
© 2003 The Biophysical Society

A New Mechanism of Model Membrane Fusion Determined from Monte Carlo Simulation

M. Müller *, K. Katsov {dagger} and M. Schick {dagger}

* Institute for Physics, Johannes Gutenberg University, Mainz, Germany; and {dagger} Department of Physics, University of Washington, Seattle, Washington

Correspondence: Address reprint requests to Michael Schick, Dept. of Physics, University of Washington, Box 351560, Seattle, WA 98195-1560. Tel.: 206-543-9948; Fax: 206-685-0635; E-mail: schick{at}phys.washington.edu.

We have carried out extensive Monte Carlo simulations of the fusion of tense apposed bilayers formed by amphiphilic molecules within the framework of a coarse-grained lattice model. The fusion pathway differs from the usual stalk mechanism. Stalks do form between the apposed bilayers, but rather than expand radially to form an axial-symmetric hemifusion diaphragm of the trans leaves of both bilayers, they promote in their vicinity the nucleation of small holes in the bilayers. Two subsequent paths are observed. 1), The stalk encircles a hole in one bilayer creating a diaphragm comprised of both leaves of the other intact bilayer, which ruptures to complete the fusion pore. 2), Before the stalk can encircle a hole in one bilayer, a second hole forms in the other bilayer, and the stalk aligns and encircles them both to complete the fusion pore. Both pathways give rise to mixing between the cis and trans leaves of the bilayer and allow for transient leakage.




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