Strain‐Promoted Cycloadditions in Lipid Bilayers Triggered by Liposome Fusion

• Published in: Angewandte Chemie International Edition Vol. 63; no. 14; pp. e202314786 - n/a
• Main Authors: Jumeaux, Coline, Spicer, Christopher D., Charchar, Patrick, Howes, Philip D., Holme, Margaret N., Ma, Li, Rose, Nicholas C., Nabarro, Joe, Fascione, Martin A., Rashid, M. Harunur, Yarovsky, Irene, Stevens, Molly M.
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 02.04.2024; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: Alkynes; Alkynes - chemistry; Azides - chemistry; bioconjugation; Biomolecules; Biosensors; Cell membranes; Chemistry; Chemistry, Multidisciplinary; Cycloaddition; Cycloaddition Reaction; Energy transfer; Fluidity; Fluorescence resonance energy transfer; FRET; Lipid Bilayers; Lipids; liposomes; Liposomes - chemistry; Medicin och hälsovetenskap; Membrane proteins; Membranes; molecular dynamics; Physical Sciences; Science & Technology; SPAAC; SPAAC; bioconjugation; AZIDE-ALKYNE CYCLOADDITION; CHOLESTEROL; liposomes; MEMBRANES; LIGATION; SURFACE; FRET; molecular dynamics; EXCHANGE
• ISSN: 1433-7851; 1521-3773; 1521-3773
• DOI: 10.1002/anie.202314786

Due to the variety of roles served by the cell membrane, its composition and structure are complex, making it difficult to study. Bioorthogonal reactions, such as the strain promoted azide‐alkyne cycloaddition (SPAAC), are powerful tools for exploring the function of biomolecules in their native environment but have been largely unexplored within the context of lipid bilayers. Here, we developed a new approach to study the SPAAC reaction in liposomal membranes using azide‐ and strained alkyne‐functionalized Förster resonance energy transfer (FRET) dye pairs. This study represents the first characterization of the SPAAC reaction between diffusing molecules inside liposomal membranes. Potential applications of this work include in situ bioorthogonal labeling of membrane proteins, improved understanding of membrane dynamics and fluidity, and the generation of new probes for biosensing assays. Upon membrane fusion and lipid mixing, the embedded functional dyes undergo cycloaddition to form the covalently bound product, resulting in the emission of FRET signal, which remains even after liposome destruction.