Paz Martínez¹ and Antoni Morros²

¹ Instituto de Biología Fundamental. Unidad de Inmunología, Universitat Autònoma de Barcelona, 08193 Bellaterra (Barcelona) Spain.

² Unitat de Biofísica. Departament de Bioquímica i de Biologia Molecular,Universitat Autònoma de Barcelona, 08193 Bellaterra (Barcelona) Spain

Received 05/06/96; Accepted 06/18/96; On-line 07/01/96

A required condition for membrane fusion between two membrane bilayers is that they have to be close to each other (87). However even though two membranes are proximal, fusion will not occur unless the bilayer structure is transiently disrupted. Such disruption may result from internal components of the membrane or from the external environment. For instance, calcium can induce membrane fusion in some bilayers rich in negatively charged lipids (88).

Phospholipids can form a variety of nonlamellar lipid assemblies. Most of these nonlamellar structures have been proposed as being involved as intermediates in membrane fusion. A qualitative concept based on "molecular shape" has successfully predicted some phase preference behaviors (89,90). Cylindrical-shaped phospholipids, like phosphatidylcholine, prefers bilayer phases. Cone shaped phospholipids, such as unsaturated ethanolamine plasmalogens, have a small polar head and a large hydrophobic region; they tend to bend the bilayer and to facilitate the formation of non-bilayer phases, like hexagonal II phase (Figure 4). Inverted cone-shaped phospholipids, such as lysophosphatidylcholine, have only one acyl chain and also tend to form curved bilayers and non-bilayer phases. The balanced co-existence of bilayer forming lipids with non-bilayer inducing lipids can result in "frustrated" structures that are in a transient and unstable situation. External changes, such as temperature increase, could alter the balance between structural factors and trigger a transition from bilayer L phase to non-bilayer HII phase (Figure 3). Alternatively, a change in the lipidic composition that would account for an increase in non-bilayer-forming lipids could also induce the phase transition. In biological membranes, proteins stabilize the bilayer phases. A decrease in the membrane protein concentration would favor the non-bilayer formation. These non-lamellar structures seem to be involved as intermediates in the membrane fusion (88).

Figure 4 - Schematic presentation of the role of lipids in the proposed mechanism of membrane fusion, via the formation of nonlamellar inverted micellar intermediates. a) human non capacitated sperm; b) apposed plasma membrane (PM) and outer acrosomal membrane (OAM) from human sperm; c) inverted micellar intermediate; d) disposition of the cone-shaped lipids (e.g. polyunsaturated phosphatidylethanolamine plasmalogen) in the formation of a rod inverted mycelle; e) formation of lamellar vesicles; f) acrosome reacted sperm. Adapted from Yeagle (88) and Verkleij (91)

In acrosomal membranes of spermatozoa, unsaturated ethanolamine plasmalogens are abundant. These lipids prefer hexagonal phases. On the other hand, cholesterol sulfate also present in these membranes, due to its large charged and hydrated polar sulfate group, is a bilayer stabilizer (49). Drastic changes in the lipidic composition during capacitation would lead to fusogenicity (Figure 4). The migration of membrane proteins from the acrosomal head towards the equatorial region could also facilitate membrane fusion.