The effect of ethanol on the phase transition temperature and the phase structure of monounsaturated phosphatidylcholines

Abstract

Previous studies from our laboratories have delineated the relationship between the acyl chain asymmetry of mixed-chain phosphatidylcholines, C(X):C(Y)PC, and the effect of ethanol concentration, [EtOH], on the main phase transition temperature, T(m), and the phase structure of the lipid bilayer composed of C(X):C(Y)PC using differential scanning calorimetry and X-ray diffraction techniques [Huang and McIntosh, Biophys. J. 72 (1997) 2702--2709]. In the present work, we have extended these studies to characterize the effect of [EtOH] on the T(m) and the phase structure of the lipid bilayer composed of sn-1 saturated/sn-2 monounsaturated phosphatidylcholines with various positions of the cis double bond. Specifically, five positional isomers of 1-eicosanoyl-2-eicosenoyl-sn-glycero-3-phosphocholines, C(20):C(20:1 Delta(n))PC with n=5, 8, 11, 13 and 17, were synthesized and studied. For C(20):C(20:1 Delta(n))PC with n=5 and 8, results from the calorimetric experiments showed that in response to various concentrations of ethanol, the change in T(m) of the lipid bilayer composed of monounsaturated lipids was characterized by a sigmoidal or biphasic profile in the plot of T(m) versus [EtOH]. In contrast, a continuous depression of the T(m) by ethanol was observed calorimetrically for C(20):C(20:1 Delta(n))PC with n> or =11. The X-ray diffraction experiments further demonstrated that C(20):C(20:1 Delta(5))PC and C(20):C(20:1 Delta(8))PC can undergo the ethanol-induced gel-to-fully interdigitated phase transition at T<T(m). Such a transition, however, was not observed for C(20):C(20:1 Delta(13))PC even at a very high ethanol concentration of 100 mg/ml. These distinct different effects of [EtOH] on the phase transition temperature and the phase structure can be attributed to various positions of the cis double bond in these monounsaturated phosphatidylcholines. And the different effects of ethanol can, in fact, be explained based on the molecular structures of these monounsaturated lipids packed in the gel-state bilayer as generated by molecular mechanics simulations. To the best of our knowledge, this is the first time that the ethanol-induced fully interdigitated bilayers are observed at T<T(m) for unsaturated phospholipids with well defined double bond positions in their sn-2 acyl chains.

Novel nail penetration enhancer containing vesicles “nPEVs” for treatment of onychomycosis

“…This could be ascribed to the gel forming potential of phospholipid-ethanol-aqueous mixtures at high ethanol concentration and the induced interdigitation of phospholipid bilayers by ethanol (McIntosh et al, 2001;Polozova et al, 2005). As also shown in Table 2, the PDI values of nPEVs did not exceed 0.4 (except for N6), suggesting a homogenous and monodisperse population.…”

“…The nPEVs dispersions displayed higher viscosity values than water owing to the existence of vesicular lamellar structures occupying high hydrodynamic volume (Bsieso et al, 2015). The significantly higher viscosity (p50.05) encountered with nPEVs prepared using 40% ethanol might be attributed to the ethanolic induced interdigitation of the phospholipid bilayer (McIntosh et al, 2001).…”

Differential Scanning Calorimetry Studies of Phospholipid Membranes: The Interdigitated Gel Phase

“…While lipids with double bonds on both chains are particularly unlikely to interdigitate, there are a few examples of interdigitation where only one chain has a double bond. For example, McIntosh et al tested the ethanol-induced interdigitation of five positional isomers of 1-eicosanoyl-2-eicosenoyl-sn-glycero-3-phosphocholine (C(20):C(20:1Δ n )PC) with a single cis bond on the sn-2 chain at position n = 5, 8, 11, 13 and 17 [109]. Ethanol-induced interdigitation can be induced when the position of the cis bond is at n= 5 or 8, but not at n= 11, 13, or 17 [109].…”

“…For example, McIntosh et al tested the ethanol-induced interdigitation of five positional isomers of 1-eicosanoyl-2-eicosenoyl-sn-glycero-3-phosphocholine (C(20):C(20:1Δ n )PC) with a single cis bond on the sn-2 chain at position n = 5, 8, 11, 13 and 17 [109]. Ethanol-induced interdigitation can be induced when the position of the cis bond is at n= 5 or 8, but not at n= 11, 13, or 17 [109]. In contrast, the fully saturated lipid with the same chain length can easily be interdigitated with a small amount of ethanol [47].…”

Mesoscopic Simulations of Biological Membranes

“…However, it is known experimentally that at low temperatures an interdigitated state, in which the terminal methyl groups of one monolayer interpenetrate the opposing layer, is also possible. This L βI phase does not spontaneously form in bilayers of symmetrical chain phospholipids, like dipalmitoylphosphatidylcholines (DPPC), [58] but can be induced by changes in the environment, like hydrostatic pressure or changes in the pH of the solution [59], or by incorporation, at the membrane interface of small amphiphilic molecules, like alcohols [60][61][62], or anesthetics [63]. Interdigitation can also be induced by changes in the lipid structure, for example by introducing an ester-linkage in the headgroup of the phospholipids [64,65].…”