Stalk-free membrane fusion of cationic lipids via an interdigitated phase

Abstract

We have studied the membrane structure of a cationic lipid (N-t-butyl-N′-tetradecyl-3-tetradecylaminopropionamidine, termed diC14-amidine) using X-ray and neutron small-angle scattering as well as dilatometry and ultrasound velocimetry. At high temperatures we found an anomalously thin lamellar fluid phase, which transforms into a loosely packed interdigitated phase below the chain melting transition. Our finding can be understood based on the specific structure of the lipid backbone, which forms a long spacer between the alkyl chains. The loose lipid packing in the gel phase leads to a significant exposure of the hydrophobic lipid core to the aqueous phase. This reduces energy penalties from the removal of water molecules during fusion and explains the untypically increased fusion properties of amidine in the gel phase. Moreover, this fusion in the gel interdigitated state apparently does not require the formation of stalk intermediate structures.