From angular to round: in depth interfacial analysis of binary phosphatidylethanolamine mixtures in the inverse hexagonal phase

Packing stress in the lipidic inverse hexagonal HII phase arises from the necessity of the ideally cylinder-shaped micelles to fill out the hexagonally-shaped Wigner–Seitz unit cell. Thus, hydrocarbon chains stretch towards the corners and compress in the direction of the flat side of the hexagonal unit cell. Additionally, the lipid/water interface deviates from being perfectly circular. To study this packing frustration in greater detail, we have doped 1-palmitoyl-2-oleoyl-sn-phosphatidylethanolamine (POPE) with increasing molar concentrations of 1,2-palmitoyl-sn-phosphatidylethanolamine (DPPE: 0 to 15 mol%). Due to its effectively longer hydrophobic tails, DPPE tends to aggregate in the corner regions of the unit cell, and thus, increases the circularity of the lipid/water interface. From small angle X-ray diffraction (SAXD) we determined electron density maps. Using those, we analysed the size, shape and homogeneity of the lipid/water interface as well as that of the methyl trough region. At 6 and 9 mol% DPPE the nanotubular water core most closely resembles a circle; further to this, in comparison to its neighbouring concentrations, the 9 mol% DPPE sample has the smallest water core area and smallest number of lipids per circumference, best alleviating the packing stress. Finally, a three-water layer model was applied, discerning headgroup, perturbed and free water, demonstrating that the hexagonal phase is most stable in the direction of the flat faces (compression zones) and least stable towards the vertices of the unit cell (decompression zones).