Lipid bilayer fusion

In membrane biology, fusion is the process by which two initially distinct lipid bilayers merge their hydrophobic cores, resulting in one interconnected structure.

If this fusion proceeds completely through both leaflets of both bilayers, an aqueous bridge is formed and the internal contents of the two structures can mix.

Exocytosis, fertilization of an egg by sperm and transport of waste products to the lysosome are a few of the many eukaryotic processes that rely on some form of fusion.

These studies have shown that divalent cations play a critical role in the fusion process by binding to negatively charged lipids such as phosphatidylserine, phosphatidylglycerol and cardiolipin.

[3] One role on these ions in the fusion process is to shield the negative charge on the surface of the bilayer, diminishing electrostatic repulsion and allowing the membranes to approach each other.

[11] Further evidence cited in favor of this theory is the fact that certain lipid mixtures have been shown to only support fusion when raised above the transition temperature of these inverted phases.

[12][13] This topic also remains controversial, and even if there is a curved structure present in the fusion process, there is debate in the literature over whether it is a cubic, hexagonal or more exotic extended phase.

[1] pH independent fusion proteins can function under neutral conditions and fuse with the plasma membrane, allowing viral entry into the cell.

In fact, there is still an active debate regarding whether SNAREs are linked to early docking or participate later in the fusion process by facilitating hemifusion.

[18] The resulting “hybridoma” from this combination expresses a desired antibody as determined by the B-cell involved, but is immortalized due to the myeloma component.

It is believed that this phenomenon results from the energetically active edges formed during electroporation, which can act as the local defect point to nucleate stalk growth between two bilayers.

Assays evaluating lipid mixing make use of concentration dependent effects such as nonradiative energy transfer, fluorescence quenching and pyrene excimer formation.

Mixing of aqueous contents from vesicles as a result of lysis, fusion or physiological permeability can be detected fluorometrically using low molecular weight soluble tracers.

Illustration of lipid vesicles fusing showing two possible outcomes: hemifusion and full fusion. In hemifusion only the outer bilayer leaflets mix. In full fusion both leaflets as well as the internal contents mix.
Schematic illustration of the process of fusion through stalk formation.
Diagram of the action of SNARE proteins docking a vesicle for exocytosis. Complementary versions of the protein on the vesicle and the target membrane bind and wrap around each other, drawing the two bilayers close together in the process. [ 15 ]
(1.) Illustration of lipid mixing assay based on Förster resonance energy transfer.
(3.) Illustration of lipid mixing assay based on Fluorescence self-quenching.
(1.) Illustration of content mixing assay based on fluorescence quencing pair ANTS/DPX.
(2.)Illustration of content mixing assay based on fluorescence enhancement pair Tb 3+ /DPA.