The fusion of cellular membranes is a central component of important biological processes, such as neural transmission and membrane trafficking. The multiple energy barriers associated with this process are overcome by biological fusion proteins, such as the Soluble NSF Attachment Protein (SNAREs). While significant effort has been devoted to characterizing the mechanisms that underlie the function of these proteins, there has been little success in developing a synthetic alternative that replicates their function. In this work, we utilize a combination of atomistic molecular dynamics simulations and experimental assays to demonstrate the ability of monolayer-protected nanoparticles to mediate the fusion of lipid membranes in a manner that mimics the function of biological fusion proteins. This is the first instance of a synthetic nanoscale device that can replicate fusion protein function.