The interactions between synthetic polycations and phospho- lipid bilayers play an important role in some biophysical applications such as gene delivery or antibacterial usage. Despite extensive investigation into the nature of these interactions, their physical and molecular bases remain poorly understood. In this Article, we present the results ofour studies on the impact of a hydrophobically modi fi ed strong polycation on the properties of a zwitter- ionic bilayer used as a model of the mammalian cellular membrane. The study was carried out using a set of complementary experimental methods and molecular dynamic (MD) simulations. A new polycation, poly(allyl- N , N

dimethyl- N -hexylammonium chloride) (polymer 3 ), was synthesized, and its interactions with liposomes composed of 2-oleoyl-1-palmitoyl- sn -glycero-3- phosphocholine (POPC) were examined using dynamic light scattering (DLS), zeta potential measurements, and cryo-transmission electron microscopy (cryo-TEM). Our results have shown that polymer 3 can e ffi ciently associate with and insert into the POPC membrane. However, it does not change its lamellar structure, as was demonstrated by cryo-TEM. The in fl uence of polymer 3 on the membrane functionality was studied by leakage experiments applying a fl uorescence dye (calcein) encapsulated in the phospholipid vesicles. The MD simulations of model systems reveal that polymer 3 promotes formation of hydrophilic pores in the membrane, thus increasing considerably its permeability.