Flip/flop diffusion rate

Finally, they proposed a model to account for together with T h that only 1/30 of the chains carry one neutral soliton and that the nuclear magnetization flows to a cylindrical relaxation core due to a soliton diffusion, through the nuclear flip/flop diffusion. An interpretation of the above observations with this model is as follows. On H NMR T]]] it is reasonable that the non-deuterated sample (l)(98/0) shows /y/w dependence due to the soliton diffusion, but not for the fully deuterated samples (2)(90/98) and (3)(20/98) in which the flip/flop diffusion rate of H is slower than a sink rate of the relaxation cores. On C NMR a situation is more complicated. In the samples (l)(98/0) and (3)(20/98), the observed frequency independency... 

Based upon a detailed analysis of reaction transients, a mechanism was proposed for chlorophyll a-photosensitized transmembrane oxidation-reduction of aqueous phase donors and acceptors that included electron transfer between juxtaposed Chi a+ r-cations and Chi a molecules as the transmembrane charge-transfer step [112]. The maximum apparent first-order rate constant for this step was 10 s , which seems large for thermal electron transfer between chlorophyll molecules located at the opposite membrane interfaces, even considering that nuclear activation barriers may be relatively small for this reaction. Transverse flip-flop diffusion of Chi b across the membrane is 10 -fold slower than transmembrane redox under these conditions, so this alternative mechanism is almost certainly unimportant. Kinetic mapping studies have shown that some of the Chi a becomes localized within the membrane at sites that are inaccessible to aqueous phase electron acceptors, presumably within the membrane interior [114]. This suggests the possibility of a transverse hopping mechanism involving electron transfer over relatively short distances from buried Chi a to interfacial Chi a+, followed by electron transfer from Chi a at the opposite interface to the buried Chi a" ". 

Problem (2) is that the spin-lattice relaxation rate of C NMR, 77c. should obey (6.14) as H NMR 77,j does, if the neutral soliton diffuses whole the sample. To investigate a role of spin flip/flop diffusion through H and C Scott and Clarke have measured 77] and 77c ll samples enriched by various ratios of C to D ( ) 98 0 (2) 90 98 and (3) 20 98 [152]. They observed ... 

NMR 7Yd shows a weak but similar frequency dependence to that of T jj. Contrary to such a successful interpretation, the magnitude of the relaxation rates TYc are an order of magnitude smaller than that of TYh, although TY and TYh are expected to have a similar magnitude provided that the hyperfine coupling constants are the same order, as suggested by the ENDOR experiment [188]. This suggests that TYcl is still under the control of the nuclear flip/flop diffusion process. 

Vesicle size, bilayer fluidity, membrane permeability, microviscosity, ability to bind small molecules, suseeptibility to pore formation, flip-flop rates, extent of water penetration, lateral amphiphile diffusion, vesiele fusion, and kinetic medium effeets (some of which will be discussed briefly below) all depend on the paeking of... 

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]. 

Exactly the same results were obtained with spin diffusion experiments performed at ZSM-39. Frequencies can be affected by spin diffusion between sites having different NMR parameters, when, for example, magnetization is transported through a solid by means of mutual spin "flip-flops" that can occur even in the absence of atomic or molecular motion. By monitoring the correlation among frequencies in the different dimensions of a multidimensional NMR experiment, it is possible to learn about the mechanisms and rates of reorientation and diffusion processes in solids (32). 

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. 

Eq. 9 leads to spin diffusion with the flip-flop rate limiting the observed T. Below 10 s, the relaxation for the A spin is limited by the relaxation sink, which corresponds to the bonded methylene carbon. The effect of the siqall deviation In the coefficients from 1.0 and 0.0 near t s 10 s is non-exponential recovery, with the negative coefficient leading to a curve which is concave downward. For the M spin, the decay Jumps from theX curve for correlation times <10 " s to the Xg curve for correlation times >10 s. 

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... 

Cells must take nutrients from their extracellular environment to grow and maintain metabolic activity. The selectivity and rate that these molecular species enter can be important in regulatory processes. The mechanisms involved depend upon the size of the molecules to be transported across the cell membrane. These biological membranes consist of a continuous double layer of lipid molecules in which various membrane proteins are imbedded. Individual lipid molecules are able to diffuse rapidly within their own monolayer however, they rarely flip-flop spontaneously between these two monolayers. These molecules are amphoteric and assemble spontaneously into bilayers when placed in water. Sealed compartments are thus formed, which reseal if torn. 

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... 

---