title: Interactions of PAMAM dendrimers with negatively charged model biomembranes.
abstract: We have investigated the interactions between cationic poly(amidoamine) (PAMAM) dendrimers of generation 4 (G4), a potential gene transfection vector, with net-anionic model biomembranes composed of different ratios of zwitterionic phosphocholine (PC) and anionic phospho-L-serine (PS) phospholipids. Two types of model membranes were used: solid-supported bilayers, prepared with lipids carrying palmitoyl-oleoyl (PO) and diphytanoyl (DPh) acyl chains, and free-standing bilayers, formed at the interface between two aqueous droplets in oil (droplet interface bilayers, DIBs) using the DPh-based lipids. G4 dendrimers were found to translocate through POPC:POPS bilayers deposited on silica surfaces. The charge density of the bilayer affects translocation, which is reduced when the ionic strength increases. This shows that the dendrimer-bilayer interactions are largely controlled by their electrostatic attraction. The structure of the solid-supported bilayers remains intact upon translocation of the dendrimer. However, the amount of lipids in the bilayer decreases and dendrimer/lipid aggregates are formed in bulk solution, which can be deposited on the interfacial layers upon dilution of the system with dendrimer-free solvent. Electrophysiology measurements on DIBs confirm that G4 dendrimers cross the lipid membranes containing PS, which then become more permeable to ions. The obtained results have implications for PAMAM dendrimers as delivery vehicles to cells.
authors.affiliation: Physical Chemistry, Center for Chemistry and Chemical Engineering, Lund University , SE-221 00 Lund, Sweden.
authors.forename: Marianna
authors.initials: M
authors.lastname: Yanez Arteta
authors.forename: Marie-Louise
authors.initials: ML
authors.lastname: Ainalem
authors.forename: Lionel
authors.initials: L
authors.lastname: Porcar
authors.forename: Anne
authors.initials: A
authors.lastname: Martel
authors.forename: Helena
authors.initials: H
authors.lastname: Coker
authors.forename: Dan
authors.initials: D
authors.lastname: Lundberg
authors.forename: Debby P
authors.initials: DP
authors.lastname: Chang
authors.forename: Olaf
authors.initials: O
authors.lastname: Soltwedel
authors.forename: Robert
authors.initials: R
authors.lastname: Barker
authors.forename: Tommy
authors.initials: T
authors.lastname: Nylander
mesh_terms: D050091:Dendrimers / Q000737:chemistry*; D008027:Light; D008051:Lipid Bilayers / Q000737:chemistry*; D033363:Neutron Diffraction; D010713:Phosphatidylcholines / Q000737:chemistry; D010718:Phosphatidylserines / Q000737:chemistry; D058525:Quartz Crystal Microbalance Techniques; D012542:Scattering, Radiation
chemical_list: D050091:Dendrimers; D008051:Lipid Bilayers; C104700:PAMAM Starburst; D010713:Phosphatidylcholines; D010718:Phosphatidylserines; C050294:1-palmitoyl-2-oleoylglycero-3-phosphoserine; C028694:1-palmitoyl-2-oleoylphosphatidylcholine