Nanoparticle-induced biomembrane fusion: unraveling the effect of core size on stalk formation

Membrane fusion in vitro is a strategy to load model or cell-derived vesicles with proteins, drugs, and genetic materials for theranostic applications. It is thus crucial to develop strategies to control the fusion process, also through synthetic fusogenic agents. Ligand-protected, membrane-penetrating gold nanoparticles (Au NPs) can facilitate membrane fusion, but the molecular mechanisms remain unresolved. Here, we tackle NP-induced stalk formation using a coarse-grained Molecular Dynamics approach and enhanced sampling techniques. We show that smaller (2 nm in diameter) NPs lead to a lower free energy barrier and higher stalk stability than larger NPs (4 nm). We demonstrate that this difference is due to a different ligand conformational freedom, which in turn depends on the Au core curvature. Our study provides precious insights into the mechanisms underlying NP-mediated membrane fusion, while our computational approach is general and applicable to studying stalk formation caused by other fusogenic agents. TOC GRAPHICS O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=197 SRC="FIGDIR/small/541080v1_ufig1.gif" ALT="Figure 1"> View larger version (93K): org.highwire.dtl.DTLVardef@137598forg.highwire.dtl.DTLVardef@d8c93eorg.highwire.dtl.DTLVardef@842de2org.highwire.dtl.DTLVardef@1e08f44_HPS_FORMAT_FIGEXP M_FIG C_FIG