Flip-flop rate, phospholipid, membrane

There is also inside-outside (transverse) asymmetry of the phospholipids. The choline-containing phospholipids (phosphatidylcholine and sphingomyelin) are located mainly in the outer molecular layer the aminophospholipids (phosphatidylserine and phos-phatidylethanolamine) are preferentially located in the inner leaflet. Obviously, if this asymmetry is to exist at all, there must be limited transverse mobility (flip-flop) of the membrane phospholipids. In fact, phospholipids in synthetic bilayers exhibit an extraordinarily slow rate of flip-flop the half-life of the asymmetry can be measured in several weeks. However, when certain membrane proteins such as the erythrocyte protein gly-cophorin are inserted artificially into synthetic bilayers, the frequency of phospholipid flip-flop may increase as much as 100-fold. 

Other ESR studies of membrane structure include the determination of phospholipid flip-flop rates (Kornberg and McConnell, 1971), studies of membrane permeability, measurements of vesicle internal volumes and transmembrane potentials (Marsh et aL, 1976 McNamee and McConnell, 1973). 

Early examples of synthetic flippases were lipidated polymers, which used bilayer distortion to bring about lipid flip-flop. In contrast to these mechanical flippases, synthetic species that apply the principles of molecular recognition to create phospholipid complexes capable of transverse diffusion have been shown to enhance lipid flip-flop in model membrane systems. Boon and Smith generated asymmetric bilayers by adding synthetic NBD phospholipids to the outer leaflet of POPC vesicles and then determined the rate of flip-flop to the inner leaflet... 

A cell membrane is illustrated in Fig. 6.1. It is built from a bilayer of lipids, usually phospholipids, associated with which are membrane proteins and polysaccharides. The antiparallel orientation of lipid layers in the bilayer is maintained due to the extremely slow flip-flop rate, i.e. the rate of diffusion transverse to the bilayer. The lipid bilayer is the structural foundation and the proteins and polysaccharides provide chemical functionality. The protein to lipid ratio shows a large variation depending on the cell, but proteins make up at least half of most cell membranes. A prominent exception is mammalian nerve cells which contain only 18 % protein (here also the lipids are sphingomyelins rather than phospholipids). Here, the primary requirement is that the cell membrane should be effective as an electrical... 

If recently synthesized phospholipid molecules remained only on the cytoplasmic surface of the ER, a monolayer would form. Unassisted bilayer transfer of phospholipid, however, is extremely slow. (For example, half-lives of 8 days have been measured across artificial membrane.) A process known as phospholipid translocation is now believed to be responsible for maintaining the bilayer in membranes (Figure 12F). Transmembrane movement of phospholipid molecules (or flip-flop), which may occur in as little as 15 seconds, appears to be mediated by phospholipid translocator proteins. One protein (sometimes referred to as flippase) that transfers choline-containing phospholipids across the ER membrane has been identified. Because the hydrophilic polar head group of a phospholipid molecule is probably responsible for the low rate of spontaneous translocation, an interaction between flippase and polar head groups is believed to be involved in phosphatidylcholine transfer. Translocation results in a higher concentration of phosphatidylcholine on the lumenal side of the ER membrane than that... 

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