Thermotropic properties of synthetic chain-substituted phosphatidylcholines: effect of substituent size, polarity, number, and location on molecular packing in bilayers

Abstract

Differential scanning calorimetry has been applied to aqueous suspensions comprised of synthetic phospholipids on whose chains reside substituents of diverse size (methyl, n-butyl, phenyl), polarity (alkyl, keto), number (one or both chains), and location (carbons 4, 6, 8, 10, 12, or 16 of 18-carbon chains). Attention focused primarily on the "main" phase transition in the lipid bilayers resulting from disordering ("melting") of the hydrocarbon tails. The thermotropic behavior revealed, among the more interesting observations, that alkyl groups at the center of the chains are far more disruptive than groups at either end. For example, distearoylphosphatidylcholine (DSPC) has a main transition temperature (Tf of 54.8 °C. Methyl substitution at carbons 4, 10, and 16 of the second chain gives Tc values of 41.5, 5.6, and 38.5 °C, respectively. Similarly, DSPC has a transition enthalpy, , of 10.6 kcal/mol. Methyl substitution at carbons 4, 10, and 16 of the second chain gives values of 8.8, 3.7, and 9.8 kcal/mol, respectively. This remarkable midchain effect is rationalized on a molecular basis and reconciled with earlier work by others showing that mobility is restricted in the first half of the chain after which motional freedom and disorder increase uniformly up to the terminal methyl. Systematic "structure-activity" studies of lipids, such as presented here, are important in testing membrane models and in controlling membrane properties through rational design of the synthetic lipids.dered state (below the transition temperature, Tc) to a more disordered, fluidlike state (above the Tc). Tracings of excess heat capacity vs temperature provide (a) Tc, the temperature at the maximum in the excess heat capacity profile, (b) ^, the total enthalpy associated with the transition, (c) MfvH, the van't Hoff enthalpy, and (d) / ^= CU, the cooperativity unit.Below rc, the "gel" phase has its hydrocarbon chains existing mainly in all-trans configurations. Both chain motion and the number of gauche linkages increase in the "liquid-crystal" phase

Membrane Properties of Archæal Macrocyclic Diether Phospholipids

“…Thermal analysis: Previous studies have shown that a methyl branchings into alkyl chains lowers the phase transition temperature (T m ), [29] and that Halobacterium lipids bearing several methyl-branched terpenyl chains exhibit no detectable gel-to-liquid crystalline phase transition over a wide range. [30] In our case the liposomes of archñal lipids (macrocyclic lipid A, diphytanylphosphatidylcholine B, diphytylphosphatidylcholine C and digeranylgeranylphosphatidylcholine D) also did not show any phase transition between À 40 and 60 8C.…”

Impact of free hydroxylated and methyl-branched fatty acids on the organization of lipid membranes

“…DSC thermograms of the lipid bilayers, composed of DMPC lipids and small amounts of incorporated fatty acids, revealed two major thermic events (Mabrey and Sturtevant, 1976;Lewis et al, 1987a,b;Menger et al, 1988). Upon an increase in temperature, an endothermic pre-transition state was found between 9 and 19 • C (data not shown), followed by the main phase transition state (T m 22-25 • C, Table 1).…”

“…The impact of both, bound and free fatty acids on the physiological properties of biological membranes was repeatedly studied by calorimetry in the last two decades (Schullery et al, 1981;Blume, 1983;Lewis et al, 1987a,b;Lewis et al, 1988;Menger et al, 1988;Langner and Hui, 2000;Funari et al, 2003;Lindström et al, 2006;Rogerson et al, 2006). For this purpose, phospholipid composed model bilayers were subjected to a temperature-induced phase transition from the relatively ordered state L ␤ gel phase to a more disordered, but biological active liquid-crystalline state, which prevails at 37 • C in humans.…”

DSC Analysis of Surfactant-Based Microstructures

“…However, the sharpness of the melting peak can be influenced by factors such as purity and crystalline defects. Ramifications near the headgroup are relatively immobilized, whereas carbon atoms near the terminal end are quite mobile [59]. Moreover, the melting temperature is less defined as the concentration of impurities increases (Fig.…”