Summary :

In vivo, membrane fusion must not occur spontaneously. Thus, membrane fusion requires a large activation energy that is overcome through the action of multiple proteins. Even though biological fusion is very complex, it results in the coalescence of both lipid bilayers that constitute the cores of the involved membranes. Therefore, the activation energy that is necessary to disrupt the leaflet arrangement during lipid bilayer fusion should be similar to that of in vivo membrane fusion.
We developed an experimental protocol which allows determining the activation energy of the fusion of lipid bilayers, thanks to Arrhenius’ law. The relative areas occupied by the polar head and hydrophobic tails of a lipid confers to it a preferential curvature, called spontaneous curvature. Investigating membranes with several lipid compositions, we found that a mismatch between the membrane’s curvature and the spontaneous curvature of the lipid affects both the activation energy and the nucleation of the process. A more negative curvature generates more hydrophobic defects in the initial “flat” membrane which leads to an increase in the frequency of fusion nucleation. During the fusion process, membrane shapes are modified and must locally adopt large curvatures. A mismatch between the spontaneous curvature of the lipid and the one it should adopt in order for fusion to proceed can inhibit the process of fusion and increase its activation energy.