Stoichiometries and Energetics of Cationic Nanoparticle-Membrane Complexes

Abstract

The nanoparticle-membrane interaction is essential to nanotheraputic design and nanotoxicity concerns. The equilibrium structure was determined for phospholipid membranes interacting with one type of nanoparticle, poly(amidoamine) dendrimers, at the atomistic and molecular scale via both experimental and theoretical approaches. The resulting dendrimer-phospholipid complex depends on both the number of primary amines per dendrimer and the dendrimer size. Large dendrimers (> 7 nm diameter) induce vesicle-encased dendrimers and significant membrane disruption. In contrast, small dendrimers (< 5 nm diameter) bind to the membrane surface without individually inducing significant membrane disruption. Techniques such as isothermal titration calorimetry (ITC), molecular dynamics (MD), and differential scanning calorimetry (DSC) were used for examination of the equilibrium structures and identifying the mechanisms of nanoparticle-induced membrane disruption.Third-, fifth-, and seventh-generation poly(amidoamine) dendrimers (G3, G5, and G7, respectively) are shown here in complexes with phospholipids. The stoichiometries and dimensions of the dendrimer-lipid complexes indicate small dendrimers (G3) saturate with lipids on a planar membrane, medium-sized dendrimers (G5) induces local membrane curvature and/or binds to multiple bilayer surfaces, and each larger dendrimer (G7) becomes encased by a lipid vesicle. These understandings will guide nanoparticle design in both medical and industrial applications.View Large Image | View Hi-Res Image | Download PowerPoint Slide