Artificial Membrane Fusion Triggered by Strain-Promoted Alkyne-Azide Cycloaddition
| Autor: | Adam J. Carr, Samuel I. Mattern-Schain, Stuart A. Whitehead, Vladimir V. Popik, Shahrina Alam, Christopher D. McNitt, Michael D. Best |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Azides
Biomedical Engineering Synthetic membrane Pharmaceutical Science Bioengineering 02 engineering and technology 010402 general chemistry 01 natural sciences Membrane Fusion Article chemistry.chemical_compound Cyclooctanes Pharmacology Liposome Fusion Aza Compounds Cycloaddition Reaction Chemistry Organic Chemistry Lipid bilayer fusion 021001 nanoscience & nanotechnology Lipids Cycloaddition 0104 chemical sciences Förster resonance energy transfer Biochemistry Alkynes Drug delivery Liposomes Biophysics Azide 0210 nano-technology Biotechnology |
| Popis: | Artificial systems for controlled membrane fusion applicable for drug delivery would ideally use triggers that are orthogonal to biology. To apply the strain-promoted alkyne-azide cycloaddition (SPAAC) to drive membrane fusion, oxo-dibenzocyclooctyne (ODIBO)-lipid 1 was designed, synthesized, and studied alongside azadibenzocyclooctyne (ADIBO)-lipids 2-4 to assess fusion with liposomes containing azido-lipid 5. Lipids 1-2 were first shown to be effective for liposome derivatization. Next, fusion was evaluated using liposomes containing 1 and varying ratios of PC and PE via a FRET dilution fusion assay, and a 1:1 PC-to-PE ratio yielded the greatest signal change attributed to fusion. Finally, lipids 1-4 were compared, and 1 yielded the greatest triggering of fusion, while 2-4 yielded varying efficacies depending on the structural features of each lipid. Fusion was further validated through STEM studies showing larger multilamellar assemblies after liposome mixing, and FRET assay results supporting the mixing of liposome aqueous contents. This work provides a platform for triggered fusion toward drug delivery applications and an understanding of the effects of lipid structure and membrane composition on fusion. |
| Databáze: | OpenAIRE |
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