Relationship of phospholipid hexagonal phases to biological phenomena

Phospholipid bilayers can undergo morphological rearrangements to other phases. The formation of one of these nonbilayer phases, the hexagonal phase, is preceded by an increase in the hydrophobicity of the bilayer surface and a destabilization of the bilayer structure. Certain membrane additives promote, while others inhibit, the formation of the hexagonal phase. Many of the molecular features that determine this phase preference are understood. Some of the properties of membranes are modulated by agents that affect the relative stability of the bilayer and hexagonal phases. Addition of bilayer stabilizers to a membrane decreases its fusogenic behaviour. One such bilayer stabilizer is cholesterol sulfate, which may function physiologically to inhibit the fusion of sperm cells. Several antiviral agents are also found to be bilayer stabilizers and some have been shown to inhibit membrane fusion phenomena. Another biological property that is modulated in a predictable manner by agents which affect the bilayer-hexagonal phase equilibrium is insulin-promoted glucose uptake in adipocytes. Bilayer stabilizers inhibit this process showing that the effects of insulin can be modulated by the bulk biophysical properties of the membrane. The activity of a number of membrane-bound enzymes is also lowered by bilayer stabilizers. Neutral and zwitterionic bilayer stabilizers are inhibitors of protein kinase C. Thus, the alteration of the bilayer-hexagonal phase transition by drugs may provide a useful parameter for predicting their effects on biological membranes.