Kinetics of DNA-Mediated Liposome Fusion with Different Binding Modes

DNA-mediated membrane fusion has great prospects in spatiotemporal control over fusion events, attributed to DNA's inherent programmability and addressability. However, the kinetics remain largely unknown, and whether zipper-like hybridization orientation is a prerequisite remains an open question. Herein, we employed a coarse-grained molecular dynamics method to systematically investigate the mechanism and kinetics of DNA-mediated liposome fusion under two distinct DNA binding modes: zipper and bridge. The results indicated that zipper mode is more favorable for fusion, while bridge mode exhibits a strong dependence on DNA linker length. The free energy barriers of liposome fusion were determined to be 10.17 <i>k</i>_B<i>T</i> for zipper mode and 12.21 <i>k</i>_B<i>T</i> for bridge mode, respectively. Furthermore, the membrane curvature and surface DNA density were identified as the main factors affecting fusion kinetics, and the optimal parameter ranges for promoting liposome fusion were also determined. These findings provide valuable insights for the rational design and optimization of DNA-mediated liposome fusion systems.