Phosphatidylethanolamine and Cholesterol Promote Hemifusion Formation: A Tug of War between Membrane Interfacial Order and Intrinsic Negative Curvature of Lipids.

Membrane fusion is an important process for the survival of eukaryotes. The shape of lipids plays an important role in fusion by stabilizing nonlamellar fusion intermediates. Lipids with intrinsic positive curvature such as lysophosphatidylcholine and others inhibit hemifusion formation, whereas lipids having intrinsic negative curvature, e.g., phosphatidylethanolamine and cholesterol (CH), are known to promote hemifusion formation. In this work, we have measured the effect of dioleoylphosphatidylethanolamine (DOPE) and CH on the depth-dependent organization, dynamics, and fusion of dioleoylphosphatidylcholine membranes. Both DOPE and CH promote hemifusion formation despite their ability to order the interfacial and acyl chain region of the membrane and block water percolation at these regions. Generally, membrane ordering and inhibition of water percolation at the acyl chain region are detrimental to membrane fusion. This clearly emphasizes the importance of intrinsic negative curvature of lipids in membrane fusion. Interestingly, DOPE and CH show differential effects on the rate of hemifusion formation, which might be owing to their ability to induce order at the interfacial region and intrinsic negative curvature. Overall, our result is significant in understanding the role of lipidic shape in membrane fusion.