Field theoretic study of bilayer membrane fusion: I. Hemifusion mechanism
Abstract
Self-consistent field theory is used to determine structural and energetic properties of intermediates and transition states involved in the standard stalk mechanism of bilayer membrane fusion. A microscopic model of flexible amphiphilic chains dissolved in hydrophilic solvent is employed to describe these self-assembled structures. We find that the barrier to formation of the initial stalk is much smaller than previously estimated by phenomenological theories and, therefore its creation it is not the rate limiting process. The relevant barrier is associated with radial stalk expansion into a hemifusion diaphragm, and it is strongly affected by both the architecture of the amphiphile and by the tension applied to the fusing membranes. This barrier is reduced when the effective spontaneous curvature of the amphiphile is made more negative, and when the tension is increased. The transition from hemifusion diaphragm to fusion pore occurs without appreciable expansion of the former. We also find that small fusion pores can be trapped in a metastable "flickering'' state at low membrane tension. At higher tensions this metastable state disappears and the fusion pore expands without bound. Successful fusion is severely limited by the architecture of the lipids. Over a small range of architectures, the initial stalk is metastable, a seemingly necessary initial state for fusion. Given an architecture for which the spontaneous curvature is too negative, either the axially-symmetric stalk becomes stable inducing a stalk phase, or linear stalks become stable and induce an inverted-hexagonal phase. However if the curvature is not sufficiently negative, metastable stalks do not form at all.Keywords
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