Domain-selective disruption and compression of phase-separated lipid vesicles by amphiphilic Janus nanoparticles

Janus nanoparticles (NPs) with anisotropic surface functionalities enable unique biomedical applications, but their interaction with the biomembranes cannot be predicted by models derived from nanoparticles with uniform surface chemistry. Here, we combine experiments with molecular dynamics (MD) simulations to investigate the interaction of amphiphilic Janus NPs, which are cationic and hydrophobic on opposite sides, with lipid vesicles exhibiting phase-separated microdomains. We demonstrate that Janus NPs preferentially bind to and extract lipids from liquid-disordered domains over a broad range of vesicle compositions. This domain-selective membrane disruption and the inter-particle attractions concurrently generate a compression force on the vesicle, causing the remaining liquid-ordered domains to bulge and the entire vesicle to wrinkle. The NP-induced membrane compression and deformation are critically driven by the surface anisotropy of the Janus NPs. The findings highlight the feasibility of using the surface anisotropy of NPs to tailor their interactions with different biological membranes.