(174af) Curvature-Driven Adsorption and Alignment of Cationic Nanoparticles to Phase Boundaries in Multicomponent Lipid Bilayers

Understanding the interactions between surface-functionalized nanoparticles (NPs) and lipid bilayers is necessary to guide the design of NPs for biomedical applications. Biological membranes are believed to contain phase-separated regions (i.e., lipid rafts) that vary in lipid composition and membrane properties and may influence interactions of NPs. Supporting this view, recent experiments found that cationic NPs adsorb more strongly to phase-separated multicomponent lipid bilayers than single-component liquid-disordered bilayers, suggesting that phase separation affects NP–bilayer interactions. Understanding the thermodynamic forces driving the preferential adsorption of NPs to phase-separated lipid bilayers is thus necessary for the rational design of nanomaterials that interact with biological membranes.

In this work, we use coarse-grained molecular dynamics simulations to investigate the effect of lipid phase behavior on the adsorption of 2-6 nm cationic NPs. We first determined the free energy change for adsorbing a NP to one-phase liquid-disordered and liquid-ordered bilayers, composed of saturated and unsaturated phospholipids, respectively. We find that that NP adsorption depends on the competition between favorable NP–lipid interactions and the unfavorable curvature deformation of the bilayer, resulting in more favorable interactions with the liquid-disordered bilayer due to its lower bending modulus. We then measured the free energy change associated with moving a NP across the surface of a phase-separated bilayer and identified a free energy minimum at the phase boundary that is attributed to the thickness gradient between the two phases that enables favorable NP–lipid interactions without necessitating large curvature deformations. Finally, we investigate the effect of NP aspect ratio on the preferential adsorption onto phase-separated bilayers by measuring the free energy associated with rotating the long axis of the NP relative to the phase boundary . The simulation results thus indicate that the intrinsic curvature present at phase boundaries drives preferential interactions with surface-adsorbed NPs, providing new insight into the forces that drive NP behavior at multicomponent, phase-separated lipid bilayers.