Stoichiometry and structure of poly(amidoamine) dendrimer- Lipid complexes

Christopher V. Kelly, Meghan G. Liroff, L. Devon Triplett, Pascale R. Leroueil, Douglas G. Mullen, Joseph M. Wallace, Sasha Meshinchi, James R. Baker, Bradford G. Orr, Mark M.Banaszak Holl

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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.

Original languageEnglish
Pages (from-to)1886-1896
Number of pages11
JournalACS Nano
Issue number7
Publication statusPublished - 28 Jul 2009
Externally publishedYes


  • Membrane disruption
  • Membrane permeability
  • Nanotoxicity
  • Phospholipid bilayer
  • Poly(amidoamine) dendrimer

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