Fractional occurrence of defects in membranes and mechanically driven interleaflet phospholipid transport

The picture of biological membranes as uniform, homogeneous bileaflet structures has been revised in recent times due to the growing recognition that these structures can undergo significant fluctuations both in local curvature and in thickness. In particular, evidence has been obtained that a temporary, localized disordering of the lipid bilayer structure (defects) may serve as a principal pathway for movement of lipid molecules from one leaflet of the membrane to the other. How frequently these defects occur and how long they remain open are important unresolved questions. In this report, we calculate the rate of molecular transport through a transient defect in the membrane and compare this result to measurements of the net transbilayer flux of lipid molecules measured in an experiment in which the lipid flux is driven by differences between the mechanical stress in the two leaflets of the membrane bilayer. Based on this comparison, we estimate the frequency of defect occurrence in the membrane. The occurrence of defects is rare: the probability of finding a defect in 1.0 microm2 of a lecithin membrane is estimated to be approximately 6.0x10(-6). Based on this fractional occurrence of defects, the free energy of defect formation is estimated to be approximately 1.0x10(-19) J. The calculations provide support for a model in which interleaflet transport in membranes is accelerated by mechanically driven lipid flow.