TY - JOUR
T1 - Stoichiometry and structure of poly(amidoamine) dendrimer- Lipid complexes
AU - Kelly, Christopher V.
AU - Liroff, Meghan G.
AU - Triplett, L. Devon
AU - Leroueil, Pascale R.
AU - Mullen, Douglas G.
AU - Wallace, Joseph M.
AU - Meshinchi, Sasha
AU - Baker, James R.
AU - Orr, Bradford G.
AU - Holl, Mark M.Banaszak
PY - 2009/7/28
Y1 - 2009/7/28
N2 - 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.
AB - 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.
KW - Membrane disruption
KW - Membrane permeability
KW - Nanotoxicity
KW - Phospholipid bilayer
KW - Poly(amidoamine) dendrimer
UR - http://www.scopus.com/inward/record.url?scp=68649116329&partnerID=8YFLogxK
U2 - 10.1021/nn900173e
DO - 10.1021/nn900173e
M3 - Article
AN - SCOPUS:68649116329
SN - 1936-0851
VL - 3
SP - 1886
EP - 1896
JO - ACS Nano
JF - ACS Nano
IS - 7
ER -