Lipids flip-flop migration

There is independent physical evidence for non-uniform distribution and restriction from transmembrane diffusion of a-Toc in lipid membranes. Differential scanning calorimetry results indicated that it partitioned into the most fluid domains in lipid vesicles. Fluorescence studies showed that a-Toc has a very high lateral diffusion rate in egg lecithin but it does not take part in transbilayer (flip-flop) migration even over many hours . It is not known if this behavior of a-Toc extends to natural biomembranes where actual structures and conditions may dramatically change migration phenomena. 

Membrane proteins show considerable mobility in the plane of the bilayer (lateral motion). There is no evidence that proteins migrate from one side of the bilayer to the other. The frequency of reorientation of lipid components (flip-flop migration) is extremely slow or nonexistent, for thermodynamic reasons. 

Note, however that the concepts about the lipid membrane as the isotropic, structureless medium are oversimplified. It is well known [19, 190] that the rates and character of the molecular motion in the lateral direction and across the membrane are quite different. This is true for both the molecules inserted in the lipid bilayer and the lipid molecules themselves. Thus, for example, while it still seems possible to characterize the lateral movement of the egg lecithin molecule by the diffusion coefficient D its movement across the membrane seems to be better described by the so-called flip-flop mechanism when two lipid molecules from the inner and outer membrane monolayers of the vesicle synchronously change locations with each other [19]. The value of D, = 1.8 x 10 8 cm2 s 1 [191] corresponds to the time of the lateral diffusion jump of lecithin molecule, Le. about 10 7s. The characteristic time of flip-flop under the same conditions is much longer (about 6.5 hours) [19]. The molecules without long hydrocarbon chains migrate much more rapidly. For example for pyrene D, = 1.4x 10 7 cm2 s1 [192]. 

Diffusivities of binary, ternary and multi-component liquid crystalline mixtures, e.g. of soap (potassium laurate (PL), water [25, 58], and lipid (dipalmitoylphosphatidylcho-line (DPPC) [25, 59] systems in lamellar, hexagonal, cubic, nematic and micellar mesophases [25,60,61] have been studied extensively by pulsed-field-gradient NMR [25] and optical techniques [62], partly because of their intimate relation to the structure and dynamical performance of biological membranes [18]. The main distinction from thermotropic phases is that for layered structures a noticeable diffusion occurs only within the layers (i.e. lateral, frequently written as Dl, but in our notation DjJ, whereas it is negligibly small and difficult to detect across the layers [60-62] (transverse migration, for bilayers denoted by flip-flop ) so the mobility is essentially two dimensional, and the anisotropy ratio is so great that it is seldom specified explicit-... 

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