Energy-minimized structures and packing states of a homologous series of mixed-chain phosphatidylcholines: a molecular mechanics study on the diglyceride moieties

Abstract

Phosphatidylcholines or C(X):C(Y)PC, quantitatively the most abundant lipids in animal cell membranes, are structurally composed of two parts: a headgroup and a diglyceride. The diglyceride moiety consists of the glycerol backbone and two acyl chains. It is the wide diversity of the acyl chains, or the large variations in X and Y in C(X):C(Y)PC, that makes the family of phosphatidylcholines an extremely complex mixture of different molecular species. Since most of the physical properties of phospholipids with the same headgroup depend strongly on the structures of the lipid acyl chains, the energy-minimized structure and steric energy of each diglyceride moiety of a series of 14 molecular species of phosphatidylcholines with molecular weights identical to that of dimyristoylphosphatidylcholine without the headgroup are determined in this communication by molecular mechanics (MM) calculations. Results of two types of trans-bilayer dimer for each of the 14 molecular species of phosphatidylcholines are also presented; specifically, the dimeric structures are constructed initially based on the partially interdigitated and mixed interdigitated packing motifs followed subsequently by the energy-minimized refinement with MM calculations. Finally, tetramers with various structures to model the lateral lipid-lipid interactions in a lipid bilayer are considered. Results of laborious MM calculations show that saturated diacyl C(X):C(Y)PC with delta C/CL values greater than 0.41 prefer topologically to assemble into tetramers of the mixed interdigitated motif, and those with delta C/CL values less than 0.41 prefer to assemble into tetramers with a repertoire of the partially interdigitated motif. Here, delta C/CL, a lipid asymmetry parameter, is defined as the normalized acyl chain length difference between the sn-1 and sn-2 acyl chains for a C(X):C(Y)PC molecule; an increase in delta C/CL value is an indication of increasing asymmetry between the two lipid acyl chains. These computational results are in complete accord with the calorimetric data presented previously from this laboratory (H-n. Lin, Z-q. Wang, and C. Huang. 1991. Biochim. Biophys. Acta. 1067:17-28).

Membrane Domain Formation, Interdigitation, and Morphological Alterations Induced by the Very Long Chain Asymmetric C24:1 Ceramide

“…According to the authors, a ratio ranging from 0.44-0.57 is typical of mixed interdigitated gel phases (56), although Lewis et al (40) showed that some PCs whose DC/CL ratios were not in the defined range were able to form mixed interdigitated gel phases (40). For NCer, DC/CL ¼ 0.41, i.e., a value consistent with a change from a partial interdigitated to a mixed interdigitated gel phase (57).…”

Effects of alcohols on the phase transition temperatures of mixed-chain phosphatidylcholines

“…Molecular mechanics (MM) calculations, which include the model building of the energy-minimized structures of monomeric lipid and higher lipid aggregates in the absence of H20, or in vacuo, and the generation of the overall steric energy associated with each of the energy-minimized structures, were carried out using Allinger's MM2 (85) program (Allinger, 1977), as described previously (Li et al, 1993). These MM calculations were performed on an IBM RS/6000 computer and Silicon Graphics/ Indigo2 workstations.…”

“…The letter 0 is used to designate the oxygen atom of one lipid's carbonyl group on the sn-I acyl chain as well as the oxygen atom of the hydroxyl group of an ethanol. C(X):C(Y)PCs were modeled similarly in vacuo, based on crystal coordinates of the same modified DMPC molecule using the procedure described earlier (Li et al, 1993;Huang and Li, 1996). The AC values, however, were distinctly different for different molecular species of C(X):C(Y)PC.…”

“…In addition, the same two types of tetrameric C(14):C(18)PC, C(13):C(19)PC, and C(12):C(20)PC, were also constructed based on the partially interdigitated motif and the fully interdigitated motif in the presence of ethanol. These two types of tetramers were the front-to-back (F-B) tetramer and the up-and-down (U-D) tetramer (Li et al, 1993;Li and Huang, 1996). As an example, the F-B and U-D tetramers for DPPC packed in the partially interdigitated motif, after energy minimization, are illustrated graphically in Fig.…”

“…3. The averaged sum of these two types of tetramers was taken to mimic, to a first approximation, the orthorhombic closed-packed structure of PC in the bilayer plane, as described previously (Li et al, 1993;Wang et al, 1995).…”