How lipid asymmetry can make vesicles fusion-competent by inhibition of the thermal undulations.

Introduction The first step in any fusion event involving biological membranes or liposomes is the close contact between the two lipid bilayers. Hefore the local collapse which gives rise to a single membrane from two membranes, the two phospholipid interfaces have to approach each other. Different interacting forces are involved. Van der Waals forces are attractive and can extend to distance of the order of 10 nm. Electrostatic forces between charged lipid head groups belonging to different membranes are generally repulsive, but the high dielectric constant of water and the screening by ions can minimize this repulsion. Moreover the lateral diffusion of phospholipids enables the charged lipids to slide away from the contact points. The so-called hydration forces are responsible for a potential barrier with a thickness of about 2-3 nm, depending on the nature of the head groups; aminophospholipids, being less hydrated than choline-containing phospholipids, are more favourable for fusion [ 1,2]. In addition to these terms, Helfrich’s group have shown that the thermal undulations of lipid bilayers correspond to a steric interaction, which can be accounted for by a repulsive force between membranes, with a typical length of interaction of the order of 10 nm [3]. Thus, van der Waals attractive forces and steric repulsions due to thermal undulations are the most important and opposing terms in fusion events and to adhere, membranes have to overcome this steric repulsion. The thermal undulations correspond to the superposition of surface fluctuations with different wavelengths. The amplitude of these waves gives an indication of the distance of steric repulsion. With a light microscope very long waves with a large amplitude are visible, but typical amplitudes are usually below the resolution of a light microscope. The thermal undulations can be inhibited in a variety of ways, for example by reducing the temperature or by stretching the membranes. Indeed, phospholipid membranes undulate because the