title: Stoichiometry and Structure of Poly(amidoamine) Dendrimer-Lipid Complexes.
abstract: The energetics, stoichiometry, and structure of poly(amidoamine) (PAMAM) dendrimer-phospholipid interactions were measured with isothermal titration calorimetry (ITC), transmission electron microscopy (TEM), atomic force microscopy (AFM), dynamic light scattering (DLS), and molecular dynamics (MD) simulations. Dendrimers of sixth-generation and smaller interacted with the lipids at an average stoichiometry and enthalpy proportional to the number of primary amines per dendrimers (4.5 ± 0.1 lipids/primary amine and 6.3 ± 0.3 kJ/mol of primary amines, respectively). Larger dendrimers, however, demonstrated a decreased number of bound lipids and heat release per primary amine, presumably due to the steric restriction of dendrimer deformation on the lipid bilayer. For example, eighth-generation PAMAM dendrimers bound to 44% fewer lipids per primary amine and released 63% less heat per primary amine as compared to the smaller dendrimers. These differences in binding stoichiometry support generation-dependent models for dendrimer-lipid complexation, which are consistent with previously observed generation-dependent differences in dendrimer-induced membrane disruption. Dendrimers of seventh-generation and larger bound to lipids with an average stoichiometry consistent with each dendrimer having been wrapped by a bilayer of lipids, whereas smaller dendrimers did not.
authors.affiliation: Applied Physics Program.
authors.forename: Christopher V
authors.initials: CV
authors.lastname: Kelly
authors.forename: Meghan G
authors.initials: MG
authors.lastname: Liroff
authors.forename: L Devon
authors.initials: LD
authors.lastname: Triplett
authors.forename: Pascale R
authors.initials: PR
authors.lastname: Leroueil
authors.forename: Douglas G
authors.initials: DG
authors.lastname: Mullen
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Wallace
authors.forename: Sasha
authors.initials: S
authors.lastname: Meshinchi
authors.forename: James R
authors.initials: JR
authors.lastname: Baker
authors.forename: Bradford G
authors.initials: BG
authors.lastname: Orr
authors.forename: Mark M
authors.initials: MM
authors.lastname: Banaszak Holl