hemifusion

Hemifusion is an intermediate state in biological membrane fusion in which two lipid bilayers have merged their outer leaflets to form a continuous outer membrane, while the inner leaflets and the contents of the two compartments remain distinct. In this state, outer-leaflet lipid mixing has occurred but a full fusion pore has not yet formed, so there is no direct continuity between the internal spaces.

Mechanistically, hemifusion is commonly described by the stalk-pore model. Fusion proteins or other fusogens bring membranes into close apposition, promote lipid curvature, and favor the formation of a lipid stalk that connects the proximal leaflets. The stalk can expand into a hemifusion diaphragm, a shared bilayer that separates the contents of the two compartments. Subsequent remodeling or rupture of this diaphragm creates a fusion pore, allowing inner leaflets to merge and enabling exchange of contents. Proteins such as SNAREs in eukaryotic vesicle fusion and viral fusion proteins in enveloped viruses can drive these steps, often with different kinetic and regulatory constraints.

Evidence for hemifusion comes from experiments that observe lipid mixing without concomitant content mixing, such as fluorescence assays showing outer-leaflet mixing preceding pore formation. Electron microscopy and biophysical studies also support the existence of a hemifused intermediate during fusion events.

Hemifusion plays roles in exocytosis, fertilization, and viral entry, and understanding it helps illuminate the fundamental mechanisms by which membranes merge. Some fusion events proceed through a rapid, direct pore-forming step without a long-lived hemifused state, depending on system specifics.