Nanoparticle Induces Membrane Fusion in a State-wise and Property-sensitive Mode

Membrane fusion is essential for many cellular physiological functions, which is modulated by highly precise molecular mechanism involving multiple energy barriers. Nanoparticles (NPs), which exhibit immense potential in the field of biomedical applications, can act as fusogen proteins to initiate and regulate membrane fusion. However, the underlying mechanisms of NP-induced membrane fusion and the molecular details involved remain largely elusive. Here, using coarse-grained molecular dynamics simulations, we systematically investigate the NP-induced membrane fusion behaviors and the influences of NP properties (size, hydrophobicity and hydrophilicity). Our results show that the vesicle-bilayer fusion induced by a hydrophobic NP is an intricately state-wise process, involving the approach and local deformation of the vesicle and bilayer bridging by the NP, the flip-flop of lipids from proximal leaflets and the formation of a fusion stalk, as well as further lipid interactions between distal leaflets and complete fusion. Moreover, we find that NP properties have distinct effects on membrane fusion and thus the optimal NP conditions for facilitating membrane fusion are obtained. Our work provides a mechanistic understanding of NP-induced membrane fusion and offers useful insights for efficient and controlled regulation of membrane fusion.