Interleaflet coupling mechanisms in bilayers of lipids and cholesterol

Whereas it appears to be generally believed that the leaflets of a phospholipid/cholesterol bilayer interact with each other in some way, the exact mechanism remains undetermined. Various suggestions have been invoked, including chain interdigitation and rapid translocation of cholesterol. There is little, if any, direct evidence supporting or excluding these hypotheses. In this letter, I examine a few different possibilities. Chain interdigitation is unlikely to be significant. Cholesterol translocation meets some, though not all, of the relevant criteria, and probably plays an important role. The simplest explanation is that the layers interact at the midplane in the same way that the ordered and disordered liquid phases common in these systems interact at their interfaces. A quick estimate of that interfacial energy shows that this is a very likely candidate. The consequences of such an energy in biological systems are briefly considered.