Membrane Potential-Mediated Vesicle Fusion for DNA Delivery Triggered by Ion Permeation

We propose a method to induce membrane fusion by adjusting the pH of the solution surrounding giant unilamellar vesicles (GUVs). This method uses charge imbalance caused by proton and hydroxide ion permeation. When the external pH was lower than that of the internal pH, GUVs became positively charged. DNA was encapsulated in carrier vesicles (large unilamellar vesicles [LUVs]) containing negatively charged acidic phospholipids. Therefore, GUVs and LUVs are electrostatically attracted, leading to full fusion, as confirmed by the fluorescence of nucleic acid-staining reagents reacting with the DNA delivered to GUVs. Full fusion was successfully induced by controlling the pH of the external vesicle solution. Using pH as a fusion trigger enables control over the timing of fusion and postfusion environments.