Lipid bilayers interdigitation

Biomimetic interfaces including lipid bilayers, hybrid bilayers, tethered bilayers as well as other interdigitated layers are composed of naturally existing constituents based mainly on the hydrophobic interaction. 

Both in the case of gastrin (53,97) and CCK (64,102) it was known that N-terminal modifications do not affect their bioactivity profile. Correspondingly, the N-terminus of gastrin and CCK was used for grafting the lipid moiety via the thiol/maleimide approach. For this purpose p-alanine was chosen as spacer of the maleimide group since the methylene moiety allows for sufficient flexibility without displacing too much the peptide chain from the double-tailed lipid. This fact was expected to allow more appropriate mimicry of natural lipids and thus, a better interdigitation with lipid bilayers. 

Figure 8 Isotropic magnetic parameter gis and Aisofor TEMPO in a series of protic and aprotic solvents and their mixtures 1, water 2, water/ethanol solution (7 3, v/v) 3, water/ethanol solution (3 7, v/v) 4, methanol 5, ethanol 6, isopropanol 1, acetone 8, olive oil/ethanol solution (9 1, w/w) 9, acetonitrile 10, olive oil 11, toluene 12, hexane. The isotropic g-factor of TEMPO in water was taken as a reference point i.e. Agiso = 0). The estimated errors are within the size of the symbols. Magnetic parameters for TEMPO partitioned in the lipid phase of the DPPC bilayer are shown as filled sguares. Parameters corresponding to the membrane in the gel phase (before the main phase transition) are marked as A and above the phase transition piso at ca. 45 °C) are marked as B. Parameters for two components of TEMPO in non-agueous phase of DPPC bilayer interdigitated by 1.2 M ethanol are marked as C and D...

There is an abrupt decrease in the lateral diffusion coefficient of DPPC upon the phase transition from the GI phase to the Gi phase. This is because the acyl-chain region is being packed even more efficiently in the Gi phase than in the GI phase, and the hydrocarbon volume in the Gi phase is smaller than in the GI phase. Also, in the Gi phase, the lipid acyl-chains from the opposing bilayer leaflets interdigitate. In order for a phospholipid molecule to diffuse it has to circumvent the nearby interdigitated molecules which hinder diffusion. 

Several other examples of drug-membrane interactions have been reported. Using X-ray diffraction techniques, interactions with tetracyclines [75], pindolol [76], and chlorpromazine [77, 78] have been described. In these studies, it was shown that in the presence of chlorpromazine the bilayer thickness or lipid head group separation in DPPC liposomes is only 30 A, which is about 20 A smaller than two fully extended DPPC molecules. Chlorpromazine produced an interdigitated phase, which is in agreement with the observed effect of chlorpromazine on the shape of erythrocytes. 

Vibrational spectroscopy also shows interactions of polyene antibiotic ion channels nystatin and amphotericin B with phospholipid bilayers (Bunow and Lewin, 1977a Iqbal and Weidekamm, 1979 Van de Ven et al., 1984). In particular, Fourier Transform Raman spectroscopy demonstrates that at high temperature, the amphotericin A complex of DPPC/cholesterol is more ordered, whereas the amphotericin B complex is as ordered as the pure lipid/cholesterol system. In the low temperature phase and in the presence of the sterol-antibiotic complex, the bilayers were suggested to be in the interdigitated state (Levin and Neil Lewis, 1990). 

At temperatures below the main transition, a basic equilibrium stracture is the subgel (crystalline) Lc phase. Its formation usually requires prolonged low-temperature incubation. In addition to the Lc phase, many intermediate stable, metastable, and transient lamellar gel structures are adopted by different lipid classes—with perpendicular or tilted chains with respect to the bilayer plane, with fully interdigitated, partially interdigitated, or noninterdigitated chains, rippled bilayers with various ripple periods, and so forth. (Fig. 1). Several polymorphic phase transitions between these structures have been reported. Well-known examples of polymorphic transitions are the subtransition (Lc- L ) and the pretransition (Lp/- Fp/) in phosphatidylcholines (33). Recently, a polymorphic transition that included rapid, reversible transformation of the usual gel phase into a metastable, more ordered gel phase with orthorhombic hydrocarbon chain-packing (so-called Y-transition) was reported to represent a common pathway of the bilayer transformation into a subgel (crystalline) Lc phase (62). 

Figure 9.10 Model of 2 x 30 DMPC bilayer in water. On the left is the initial conformation of the starting bilayer with all-frarw lipids note the partly interdigitated bilayer. On the right is the same system after 2 ns at constant volume note the presence of numerous gauche conformers and...

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