Curvature-driven adsorption of cationic nanoparticles to phase boundaries in multicomponent lipid bilayers

Understanding the interactions between surface-functionalized gold nanoparticles (NPs) and lipid bilayers is necessary to guide the design of NPs for biomedical applications. 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. In this work, we use coarse-grained molecular dynamics simulations to investigate the effect of lipid phase behavior on the adsorption of small cationic NPs. We first determined the free energy change for adsorbing a NP to one-phase liquid-disordered and one-phase liquid-ordered bilayers. The simulations indicate that NP adsorption depends on a competition between favorable NP-lipid interactions and the unfavorable curvature deformation of the bilayer, resulting in stronger 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. The free energy minimum is attributed to the thickness gradient between the two phases that enables favorable NP-lipid interactions without necessitating large curvature deformations. 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.