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

Abstract

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.