Lipids interdigitation

Tarsal, metatarsal, caudal, interdigital and preorbital glandular structures have been described in the black-tailed deer, Odocoileus hemionus columbianus. The tarsal organ received considerable attention from chemists and behavioral scientists during the early years of chemical research on mammalian semiochemicals. The major constituent of the complex mixture of volatile compounds associated with the tarsal hair tuft of this mule deer, (Z)-6-dodecen-4-olide [ 125], was subsequently found to be a mixture of the R and S enantiomers in a ratio of 89 11 respectively [ 126]. It was later found that this compound does not originate in the tarsal structure itself, but that it is extracted from the animal s urine by the tarsal hair tuft, which is specially adapted to extract lipids from urine [127]. 

Simon, S.A. and T.J. McIntosh. 1984. Interdigitated hydrocarbon chain packing causes the biphasic transition behavior in lipid/alcohol suspensions. Biochim Biophys Acta 773 169-172. 

These results clearly show that our solvent displacement process leads to the formation of AmB-lipid structures that are different from the ribbon-like ones described by Janoff et al. (11,21) for the same composition. Our observations are consistent with a model of the antibiotic intercalated between the phospholipids in an interdigitated structure for the molar ratio DMPC/DMPG/AmB 7/3/5. The strong interaction between AmB and... 

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. 

Thus, the partial or total removal of the interdigitation of the lipid alkyl chains by cholesterol seems to be an important factor in determining the ability of the ketone molecule to place the C = O group close to the polar interface, at low temperatures. As the interdigitation is removed, the contact between the C = O group of the 9HP molecule and the solvent increases. 

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. 

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. 

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). 

Raffy, S. and Teissie, J., Electroinsertion of glycophorin A in interdigitation-fusion of giantunilameUar lipid vesicles, J. Biol. Chem., Ill, 25524, 1997. 

DSC provides useful information in the design of liposomal formulations for incorporating labdanes while phenomena like interdigitation should be taken into account when designing lipid carriers. It is obvious from the above paradigms that bioactivc natural compounds can demonstrate improved pharmacological responses and their biodistribution and pharmacokinetic profiles can be controlled by designing suitable carrier for each compound. 

---