Structure and interaction in 2D organized assemblies of cationic lipids with tryptophan: an experimental and computational investigation

Molecular association of lipid membranes is an important tool to understand their biological functions. Engineered nano/microscopic lipid surface structures enable controlled surface properties such as adhesion, wetting and molecular recognition, correlated to the surface topography, molecular structure and interactions. In this work, patterned nanometer scale 2D lipidic channels from two cationic phospholipids, namely, 1,2-distearoyl-sn-glycero-3-ethylphosphocholine (EPC) and 1,2-dioleoyl-sn-glycero-3-ethylphosphocholine (EPCU) are reported along with the zwitter-ionic lipid 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) as a reference. Atomic force microscopy was used to probe the exotic 2D lipidic channels formed on the mica substrate. Analyzing the isotherms comprising 2D surface pressure as a function of the mean molecular area provided insights into hydrocarbon chain ordering and packing, lateral compressibility/elasticity, and head group influence on that one leaflet of a bilayer. The condensed phase surface topography revealed 2D multiple-fold lipidic vesicles fused anisotropically into regular ordered channels of 30-50 nm height and 300-500 nm width. The results revealed condensation of the monolayer into higher ordered phases as a function of the chemical structure of the lipids. The chemical reactivity and electronic properties of the pure lipids and lipids in association with tryptophan amino acids were unravelled adopting density-functional theory (DFT) calculations. The packing and surface elastic properties of the lipid monolayers during interaction with tryptophan revealed phase separation in the surface architecture as a result of the occurrence of predominant electrostatic, hydrogen-bonding and hydrophobic interactions between the components, as revealed from the DFT results.