Quantifying the Electrostatics of Polycation–Lipid Bilayer Interactions

Mechanistic insight into how polycations disrupt and cross cell membranes is needed for understanding and controlling polycation–membrane interactions, yet such information is surprisingly difficult to obtain at the molecular level. We use second harmonic and vibrational sum frequency generation spectroscopies along with quartz crystal microbalance with dissipation monitoring and computer simulations to quantify the interaction of poly(allylamine) hydrochloride (PAH) and its monomeric precursor allylamine hydrochloride (AH) with lipid bilayers. We find PAH adsorption to be reversible and nondisruptive to the bilayer under the conditions of our experiments. With an observed free adsorption energy of −52.7 ± 0.6 kJ/mol, PAH adsorption was found to be surprisingly less favorable relative to AH (−14.6 ± 0.4 kJ/mol) when considering a simple additive model. By experimentally quantifying the number of adsorbates and the average amount of charge carried by each adsorbate, we find that the PAH is associated with ...