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Biophys. J. BioFAST: First Published November 4, 2005. doi:10.1529/biophysj.105.071092
© 2005 by the Biophysical Society.

A more recent version of this article appeared on February 1, 2006.
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MEMBRANES

Field Theoretic Study of Bilayer Membrane Fusion:II. Mechanism of a Stalk-Hole Complex

Kirill Katsov 1, Marcus Mueller 2 and Michael Schick 3*

1 University of California, Santa Barbara
2 Institut fur Theoretische Physik, Goettingen, GERMANY
3 University of Washington, Seattle

* To whom correspondence should be addressed. E-mail: schick{at}phys.washington.edu.

Submitted on July 20, 2005
Revised on September 10, 2005
Accepted on 12 October 2005


  Abstract
We use self-consistent field theory to determine structural and energetic properties of intermediates and transition states involved in bilayer membrane fusion. In particular, we extend our original calculations from those of the standard hemifusion mechanism, which was studied in detail in the first paper of this series, to consider a possible alternative to it. This mechanism involves non-axial stalk expansion, in contrast to the axially symmetric evolution postulated in the classical mechanism. Elongation of the initial stalk facilitates the nucleation of holes and leads to destabilization of the fusing membranes via the formation of a stalk-hole complex. We study properties of this complex in detail, and show how transient leakage during fusion, previously predicted and recently observed in experiment, should vary with lipid architecture and tension. We also show that the barrier to fusion in the alternative mechanism is lower than that of the standard mechanism by a few kT over most of the relevant region of system parameters, so that this alternative mechanism is a viable alternative to the standard pathway. We emphasize that any mechanism, such as this alternative one, which affects even modestly the line tension of a hole in a membrane affects greatly the ability of that membrane to undergo fusion.

Key Words: field theory, fusion stalk, hemifusion, leakage, membrane fusion, membrane modeling




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Copyright © 2005 by the Biophysical Society.