Rupture\nof Lipid Membranes Induced by Amphiphilic\nJanus Nanoparticles

Abstract

The\nsurface coatings of nanoparticles determine their interaction\nwith biomembranes, but studies have been limited almost exclusively\nto nanoparticles with a uniform surface chemistry. Although nanoparticles\nare increasingly made with complex surface chemistries to achieve\nmultifunctionalities, our understanding of how a heterogeneous surface\ncoating affects particle–biomembrane interaction has been lagging\nfar behind. Here we report an investigation of this question in an\nexperimental system consisting of amphiphilic “two-faced”\nJanus nanoparticles and supported lipid membranes. We show that amphiphilic\nJanus nanoparticles at picomolar concentrations induce defects in\nzwitterionic lipid bilayers. In addition to revealing the various\neffects of hydrophobicity and charge in particle–bilayer interactions,\nwe demonstrate that the Janus geometrythe spatial segregation\nof hydrophobicity and charges on particle surfacecauses nanoparticles\nto bind more strongly to bilayers and induce defects more effectively\nthan particles with uniformly mixed surface functionalities. We combine\nexperiments with computational simulation to further elucidate how\namphiphilic Janus nanoparticles extract lipids to rupture intact lipid\nbilayers. This study provides direct evidence that the spatial arrangement\nof surface functionalities on a nanoparticle, rather than just its\noverall surface chemistry, plays a crucial role in determining how\nit interacts with biological membranes.