ABSTRACT
We recently reported a DNA-programmed fusion cascade enabling the use of liposomes as nanoreactors for compartmentalized chemical reactions. This communication reports an alternative and robust strategy based on lipidated peptide nucleic acids (LiPs). LiPs enabled fusion of liposomes with remarkable 31% efficiency at 50 °C with low leakage (5%).
Subject(s)
Liposomes/chemistry , Membrane Fusion , Peptide Nucleic Acids/chemistry , Base Sequence , DNA/chemistry , Lipids/chemistry , Polyethylene Glycols/chemistry , RNA/chemistryABSTRACT
The fusion of biomembranes with release of encapsulated content in a controlled way is crucial for cell signaling, endo- and exocytosis and intracellular trafficking. Programmable fusion of liposomes and an efficient mixing of their contents have the potential to enable the study of chemical and enzymatic processes in a confined environment and under crowded conditions outside biological systems. We report on DNA-controlled fusion of lipid bilayer membranes using lipid-nucleic acid conjugates (LiNAs) to mediate lipid and content mixing of liposomes. Screening of different membrane anchor and linker structures as well as incubation temperatures led to significantly improved fusion and content mixing compared to reported systems. LiNA designs were optimized by changing lipophilic moieties as membrane anchors, PEG-spacer patterns and by introducing locked nucleic acid (LNA) modifications. Liposome fusion induced by complementary LiNAs results in remarkable efficient content mixing at 37 °C and 50 °C (up to 70%) with low leakage (≤5%).
