Structural behavior of amphiphilic polyion complexes interacting with saturated lipid membranes investigated by coarse-grained molecular dynamic simulations

Neutral polyelectrolyte complexes (PECs) made from an amphiphilic multiblock copolymer of type (AnBn)m and an oppositely charged polyion and interacting with a dipalmitoylphosphatidylcholine (DPPC) lipid membrane have been examined employing a coarse-grained model with implicit solvent and molecular dynamics simulations. One systematically explored the influence of the size of the hydrophobic block B and of the number of these blocks per chain on the PEC tendency to adhere to the membrane surface and to intercalate into the membrane core. Simulation results showed that PECs bound irreversibly to the lipid bilayer without polyion unwinding from the complex and the adsorbed conformation was strongly affected by the size of the hydrophobic block B. The adsorption kinetics at low B size were characterized by a relaxation phase dominated by the spreading of PEC constituents along the outer leaflet of the membrane. Upon increasing the size of the hydrophobic block B to reach core–shell organization of the free PEC, the relaxation pathway of the complex corona in close contact with the headgroup lipids facilitated the transient exposure of the PEC hydrophobic core to the lipids and its subsequent cooperative internalization and solubilization in the membrane inner part associated with an internal reorganization of the lipid bilayer. In the generated snorkeling-type conformation, the charged blocks A and the oppositely charged polyion were confined to the headgroup region of the top leaflet, without spontaneous flipping to the headgroup region of the distal leaflet.