(469c) Assembly of Charged Nanoparticles on Phase-Separated Lipid Bilayers

The interactions between charged nanoparticles and lipid bilayers have been investigated extensively in both computational and experimental studies due to the relevance of these materials for drug delivery and other biomedical applications. However, most mechanistic studies have focused on simplified model membranes containing a single lipid component in the fluid phase. While useful, these model systems neglect the compositional heterogeneities associated with biologically relevant membranes. One such heterogeneity is the presence of lipid rafts, or phase-separated domains enriched in ordered lipids and cholesterol. Recent experimental work has suggested that charged nanoparticles bind more strongly to membranes containing rafts, although the mechanism underlying this increased binding is unknown. In this work, we use coarse-grained molecular dynamics simulations and enhanced sampling techniques to investigate the adhesion of charged nanoparticles to phase-separated lipid membranes as models for membranes containing lipid rafts. We find that nanoparticle binding is enhanced on single-component disordered lipid bilayers due to the ability of the membrane to deform to increase favorable lipid-nanoparticle interactions. In phase-separated bilayers, nanoparticles are driven to assemble at lipid raft boundaries due to the thickness difference between the ordered and disordered domains which reduces the elastic deformation of the bilayer upon binding. We further find that collections of nanoparticles can assemble at raft boundaries despite repelling each other in solution. These results provide new insight into the interactions of charged nanoparticles with more complex membrane compositions and suggests design guidelines for directing the assembly of nanoparticles on complex membranes.