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Abstract
Lipid bilayer fusion is thought to involve formation of a local hemifusion connection,
referred to as a fusion stalk. The subsequent fusion stages leading to the opening
of a fusion pore remain unknown. The earliest fusion pore could represent a bilayer
connection between the membranes and could be formed directly from the stalk. Alternatively,
fusion pore can form in a single bilayer, referred to as hemifusion diaphragm (HD),
generated by stalk expansion. To analyze the plausibility of stalk expansion, we studied
the pathway of hemifusion theoretically, using a recently developed elastic model.
We show that the stalk has a tendency to expand into an HD for lipids with sufficiently
negative spontaneous splay, (~)J(s)< 0. For different experimentally relevant membrane
configurations we find two characteristic values of the spontaneous splay. (~)J*(s)
and (~)J**(s), determining HD dimension. The HD is predicted to have a finite equilibrium
radius provided that the spontaneous splay is in the range (~)J**(s)< (~)J(s)<(~)J*(s),
and to expand infinitely for (~)J(s)<(~)J**(s). In the case of common lipids, which
do not fuse spontaneously, an HD forms only under action of an external force pulling
the diaphragm rim apart. We calculate the dependence of the HD radius on this force.
To address the mechanism of fusion pore formation, we analyze the distribution of
the lateral tension emerging in the HD due to the establishment of lateral equilibrium
between the deformed and relaxed portions of lipid monolayers. We show that this tension
concentrates along the HD rim and reaches high values sufficient to rupture the bilayer
and form the fusion pore. Our analysis supports the hypothesis that transition from
a hemifusion to a fusion pore involves radial expansion of the stalk.