Scanning calorimetric study of fully hydrated asymmetric phosphatidylcholines with one acyl chain twice as long as the other

Abstract

The asymmetric C(18):C(10)PC molecules are known by X-ray diffraction to self-assemble, in excess water, into a lamellar structure known as the mixed interdigitated bilayer at T < Tm. In this structure, the long C(18)-acyl chain is interdigitated fully across the entire hydrocarbon width of the bilayer, while the shorter C(10)-acyl chain, which is about half as long as the C(18)-acyl chain, packs end to end with a C(10)-acyl chain of another lipid molecule in the opposing bilayer leaflet. We have synthesized the following asymmetric phosphatidylcholines (PC''s): C(16):C(9)PC, C(16):C(10)PC, C(18):C(10)PC, C(18):C(11)PC, C(20):C(11)PC, C(20):C(12)PC, C(22):C(12)PC, C(22):C(13)PC, C(8):C(18)PC, and C(10):C(22)PC. These 10 asymmetric phosphatidylcholines have a common characteristic; i.e., the length of the longer extended acyl chain is about twice as long as that of the shorter acyl chain. On the basis of the known lamellar structure of C(18):C(10)PC, we anticipate that these asymmetric phosphatidylcholines will also form mixed interdigitated bilayers. We have employed high-resolution differential scanning calorimetry (DSC) to investigate the thermotropic behavior of liposomes prepared from these asymmetric phosphatidylcholines. If our anticipation is correct, one would find that the thermodynamic data (Tm, .DELTA.H, or .DELTA.S) associated with the main thermal phase transitions of these assymetric phosphatidylcholine dispersions will fit into a continuous curve as they are plotted as a function of the hydrocarbon width of the putative mixed interdigitated bilayer. Experimental data presented in this paper indeed bear this out. For comparison, a DSC study of multilamellar dispersions prepared from a series of saturated symmetric phosphatidylcholines has also been carried out. The thermodynamic data associated with the main phase transition of these symmetric phosphatidylcholine dispersions are shown to be distinctively different from those of asymmetric phosphatidylcholine species with the same molecular weight. Saturated symmetric phosphatidylcholines are well-known to form normal noninterdigitated bilayers in excess water. When thermodynamic data are plotted against the hydrocarbon width of the normal bilayer, they all fall on a smooth continuous curve. This curve, however, is distinctively different from that fitted by the corresponding data derived from liposomes of asymmetric phosphatidylcholines. Our results can thus be taken as strong evidence to argue for the formation of mixed interdigitated bilayers by the asymmetric phosphatidylcholines under study.