Cholesterol-containing liposomes decorated with Au nanoparticles as minimal tunable fusion machinery

Abstract

Membrane fusion is essential for the basal functionality of eukaryotic cells. In physiological conditions, fusion events are regulated by a wide range of specialized proteins, as well as by a finely tuned local lipid composition and ionic environment. SNARE proteins, for example, provide the mechanical energy necessary to achieve vesicle fusion in neuromediator release, and their action is assisted by other soluble proteins, membrane cholesterol, and calcium ions. Similar cooperative effects must be explored when considering synthetic approaches to achieve controlled and selective membrane fusion. Here we show that liposomes decorated with amphiphilic Au nanoparticles (AuLips) can act as minimal tunable fusion machinery. AuLips fusion is triggered by divalent ions, while the number of fusion events dramatically depends on, and can be finely tuned by, the liposome cholesterol content. Our results, obtained via a combination of experimental (Quartz-Crystal-Microbalance with Dissipation monitoring, Fluorescence assays, Small-Angle X-ray Scattering) and computational techniques (Molecular Dynamics with coarse-grained resolution), reveal new mechanistic details on the fusogenic activity of amphiphilic Au nanoparticles in synergy with membrane cholesterol, and demonstrate the ability of these synthetic nanomaterials to induce fusion regardless of the divalent ion used (Ca2+or Mg2+). This evidence provides a novel contribution to the development of new artificial fusogenic agents for next-generation biomedical applications that require tight control of the rate of fusion events (e.g., targeted drug delivery).