Insight into the Molecular Mechanism of Surface Interactions of Phosphatidylcholines─Langmuir Monolayer Study Complemented with Molecular Dynamics Simulations

Abstract

Mutual interactions between components of biological membranes are pivotal for maintaining their proper biophysical properties, such as stability, fluidity, or permeability. The main building blocks of biomembranes are lipids, among which the most important are phospholipids (mainly phosphatidylcholines (PCs)) and sterols (mainly cholesterol). Although there is a plethora of reports on interactions between PCs, as well as between PCs and cholesterol, their molecular mechanism has not yet been fully explained. Therefore, to resolve this issue, we carried out systematic investigations based on the classical Langmuir monolayer technique complemented with molecular dynamics simulations. The studies involved systems containing 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) analogues possessing in the structure one or two polar functional groups similar to those of DPPC. The interactions and rheological properties of binary mixtures of DPPC analogues with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and cholesterol were compared with reference systems (DPPC/POPC and DPPC/cholesterol). This pointed to the importance of the ternary amine group in PC/cholesterol interactions, while in PC mixtures, the phosphate group played a key role. In both cases, the esterified glycerol group had an effect on the magnitude of interactions. The obtained results are crucial for establishing structure-property relationships as well as for designing substitutes for natural lipids.

Figure 1

Chemical structures of the investigated compounds along with a comparison of the functional groups present in their molecules (symbol means the presence, while □ means the absence of the selected functional group). Abbreviations: DPPC—1,2–dipalmitoyl–sn–glycerol–3–phosphocholine; DPTAP—1,2–dipalmitoyl–3–trimethylammonium–propane chloride; DPPA—sodium 1,2–dipalmitoyl–sn–glycero–3–phosphate; DPG—1,2–dipalmitoyl–sn–glycerol; DHDP—sodium dihexadecylphosphate; DODAC—dimethyldioctadecylammonium chloride.

Figure 2

Surface behavior of DPPC and its analogues in Langmuir monolayers: (a) experimental surface pressure–area per molecule isotherms measured at 20 °C and (b) calculated compressibility moduli–surface pressure curves.

Figure 3

DPPC and its analogues in binary films with Chol: (a) the excess Gibbs free energy of mixing and (b) changes in compressibility moduli values with respect to a monolayer of the respective DPPC analogue versus film composition at a surface pressure of 35 mN/m.

Figure 4

DPPC and its analogues in binary films with POPC: (a) excess Gibbs free energy of mixing and (b) changes in compressibility moduli values in reference to the POPC monolayer versus film composition at a surface pressure of 35 mN/m.

Figure 5

Electron density profiles across systems simulated with MD: (a) DPPC/POPC, (b) DPPA/POPC, and (c) DHDP/POPC.

Figure 6

Radial distributions function of Na⁺ ions around the nonbridging oxygens in a phosphate group of the (a) DPPA/POPC and (b) DHDP/POPC systems.

Figure 7

Radial distribution functions of Na⁺ ions around the carbonyl oxygen atoms of (a) the DPPA/POPC and (b) the DHDP/POPC systems.