title: Quantifying the Electrostatics of Polycation-Lipid Bilayer Interactions.
abstract: 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 only 70% of the positive charges it could hold while the AH remains mostly charged while attached to the membrane. Simulations indicate that PAH pulls in condensed counterions from solution to avoid charge-repulsion along its backbone and with other PAH molecules to attach to, and completely cover, the bilayer surface. In addition, computations indicate that the amine groups shift their pKavalues due to the confined environment upon adsorption to the surface. Our results provide experimental constraints for theoretical calculations, which yield atomistic views of the structures that are formed when polycations interact with lipid membranes that will be important for predicting polycation-membrane interactions.
authors.affiliation: Department of Chemistry, Northwestern University , 2145 Sheridan Road, Evanston, Illinois 60208, United States.
authors.forename: Julianne M
authors.initials: JM
authors.lastname: Troiano
authors.affiliation: Department of Chemistry, Northwestern University , 2145 Sheridan Road, Evanston, Illinois 60208, United States.
authors.forename: Alicia C
authors.initials: AC
authors.lastname: McGeachy
authors.affiliation: Department of Chemistry, Northwestern University , 2145 Sheridan Road, Evanston, Illinois 60208, United States.
authors.forename: Laura L
authors.initials: LL
authors.lastname: Olenick
authors.affiliation: Department of Chemistry, University of Wisconsin , 680 North Park Street, Madison, Wisconsin 53706, United States , and.
authors.forename: Dong
authors.initials: D
authors.lastname: Fang
authors.affiliation: Department of Chemistry, University of Wisconsin , 680 North Park Street, Madison, Wisconsin 53706, United States , and.
authors.forename: Dongyue
authors.initials: D
authors.lastname: Liang
authors.affiliation: Department of Chemistry, University of Wisconsin , 680 North Park Street, Madison, Wisconsin 53706, United States , and.
authors.forename: Jiewei
authors.initials: J
authors.lastname: Hong
authors.affiliation: Environmental Chemistry and Technology Program, University of Wisconsin , 1415 Engineering Drive, Madison, Wisconsin 53706, United States.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Kuech
authors.affiliation: Environmental Chemistry and Technology Program, University of Wisconsin , 1415 Engineering Drive, Madison, Wisconsin 53706, United States.
authors.forename: Emily R
authors.initials: ER
authors.lastname: Caudill
authors.affiliation: Department of Chemistry, University of Wisconsin , 680 North Park Street, Madison, Wisconsin 53706, United States , and.|Environmental Chemistry and Technology Program, University of Wisconsin , 1415 Engineering Drive, Madison, Wisconsin 53706, United States.
authors.forename: Joel A
authors.identifier: 0000-0002-3918-1860
authors.initials: JA
authors.lastname: Pedersen
authors.affiliation: Department of Chemistry, University of Wisconsin , 680 North Park Street, Madison, Wisconsin 53706, United States , and.
authors.forename: Qiang
authors.identifier: 0000-0001-6214-5211
authors.initials: Q
authors.lastname: Cui
authors.affiliation: Department of Chemistry, Northwestern University , 2145 Sheridan Road, Evanston, Illinois 60208, United States.
authors.forename: Franz M
authors.identifier: 0000-0001-8569-4045
authors.initials: FM
authors.lastname: Geiger