Membrane fusion (Fig. 11.1) is an essential event in many biological

processes of eukaryotic cells (Jahn et al., 2003), such as for

instance, in the vesicular release of hormones. Membrane fusion

is thought to begin with the formation of a hemifusion stalk,

an intermediate structure connecting the outer leaflets of fusing

membranes (for a review see Chernomordik and Kozlov, 2008).

The hemifusion stalk then develops into a fusion neck (pore), the

membrane bilayer channel connecting a spherical vesicle and a

plasma membrane, through which cargo molecules may diffuse

from the vesicle lumen into the cell exterior (Jorgacˇevski et al.,

2010). After formation, the fusion neck either closes and allows

the vesicle to be reused in another round of (transient) exocytosis

(Ceccarelli et al., 1973), or it fully opens, leading to full fusion

exocytosis, that is, complete merging of the vesicle membrane

with the target plasma membrane (see Heuser and Reese, 1973,

and Fig. 11.1). The mechanisms by which the initial fusion neck

between the vesicle and the plasma attains stability are still

poorly understood (Jorgacˇevski et al., 2010). Formation of the

fusion neck at first glance may be considered to be energetically

unfavourable by the argument that the repulsive electrostatic forces

between two closely opposed phospholipid bilayers need to be

overcome in order to reach metastable transition states leading

to fusion neck formation (Kozlov and Markin, 1983). However,

in cellular systems the repulsive electrostatic force between like-

charged membrane surfaces can be reduced or even changed into

an attractive force, for example, by protein-mediated interactions

between like-charged membrane surfaces, where the proteins (or

some other biological nanoparticles, such as lipoproteins) should

have a distinctive internal charge distribution (see Chapter 14 and

Kim et al., 2008; May et al., 2008; Urbanija et al., 2007, 2008a,b).

Another example of possible mediators that may reduce the energy

barrier between the vesicles and the target plasma membrane in

regulated exocytosis is soluble N-ethylmaleimide-sensitive factor attachment protein (SNARE) receptor (Duman and Forte, 2003; Jahn

and Scheller, 2006; Martens et al., 2007).