Self-consistent-field modeling of complex molecules with united atom detail in inhomogeneous systems. Cyclic and branched foreign molecules in dimyristoylphosphatidylcholine membranes

Abstract

We have developed a detailed self-consistent-field model for studying complex molecules in inhomogeneous systems, in which all the molecules are represented in a detailed united atom description. The theory is in the spirit of the approach developed by Scheutjens and co-workers for polymers at interfaces and self-assembly of surfactants and lipids into association colloids. It is applied to lipid membranes composed of dimyristoylphosphatidylcholine ͑DMPC͒. In particular, we looked at the incorporation of linear, branched, and cyclic molecules into the lipid bilayers being in the liquid phase. Detailed information on the properties of both the lipids and the additives is presented. For the classes of linear and branched alcohols and phenol derivatives we find good correspondence between calculated partition coefficients for DMPC membranes and experimental data on egg-yolk PC. The calculated partitioning of molecules of isomers, containing a benzene ring, two charged groups ͑one positive and one negative͒ and 16 hydrocarbon segments, into DMPC membranes showed variations of the partition coefficient by a factor of 10 depending on the molecular architecture. For zwitterionic additives we find that it is much more difficult to bring the positive charge into the membrane core than the negative one. This result can be rationalized from information on the electrostatic potential profile of the bare membrane, being positive in both the core and on the membrane surface but negative near the position of the phosphate groups. For several tetrahydroxy naftalenes we found that, although the partition coefficient is barely influenced, the average orientation and position of the molecule inside the membrane is strongly dependent on the distribution of the hydroxyl groups on the naphthalene rings. The orientation changes from one where the additive spans the membrane when the hydroxyls are positioned on ͑2,3,6,7͒ positions, to an orientation with the rings parallel to the membrane surface and located near the head grouphydrophobic core interface for the hydroxyls at the ͑1,3,5,7͒ positions. We propose that, when our model is used in combination with octanol/water partitioning data, a very accurate prediction is possible of the affinity of complex molecules for lipid membranes.

Chemical Speciation of Organics and of Metals at Biological Interphases

“…If zwitterionic xenobiotics are introduced into the membrane, their magnitude of partitioning is strongly dependent on the position of the ionic groups, as was shown by self-consistent field modelling for a series of hypothetical model compounds composed of a phenyl ring substituted with propyl groups and one positively charged amino group and one corresponding negatively charged group [175] (see also Chapter 2 in this volume). The positive amino group is located at the outer side of the hydrophobic core, close to the phosphate groups.…”

Biological and synthetic membranes: What can be learned from a coarse-grained description?

“…Meijer et al [ 300] used extensions of the lattice mean-field model to study inclusions of foreign molecules in bilayer membranes utilizing a detailed description of both rigid and flexible molecules with, and without, electrostatic interactions. To handle the rigid inclusions whose segment structure is not necessarily commensurate with the underlying tetragonal lattice (used to generate RIS hydrocarbon chain configurations), the authors must make several approximations to preserve efficiency of the propagator scheme.…”

Coexistence of Spheres and Rods in Micellar Solution of Dodecyldimethylamine Oxide

“…This choice is not critical in the following results, and we refer to the literature for a more detailed motivation for this. 52 The SCF Approach Tailored to Surfactant Systems. In each coordinate r, i.e., value of z in the 1D theory and for each set (z,R) in the 2D theory, there exists for each segment type B in the system (here B ) C, H, W) on one hand a potential field u B (r) and complementary to this an observable volume fraction B (r).…”