Strain-Promoted Cycloadditions in Lipid Bilayers Triggered by Liposome Fusion

TY - JOUR

T1 - Strain-Promoted Cycloadditions in Lipid Bilayers Triggered by Liposome Fusion

AU - Jumeaux, Coline

AU - Spicer, Christopher D.

AU - Charchar, Patrick

AU - Howes, Philip D.

AU - Holme, Margaret N.

AU - Ma, Li

AU - Rose, Nicholas C.

AU - Nabarro, Joe

AU - Fascione, Martin A.

AU - Rashid, M. Harunur

AU - Yarovsky, Irene

AU - Stevens, Molly M.

N1 - Funding Information: C.J. and M.M.S. gratefully acknowledge financial support from the Rosetrees Trust. M.M.S. acknowledges support from the Engineering and Physical Sciences Research Council (EPSRC) through the Interdisciplinary Research Centre (IRC) “Early Warning Sensing Systems for Infectious Diseases” (EP/K031953/1) and from the grant “Bio‐functionalised Nanomaterials for Ultrasensitive Biosensing” (EP/K020641/1). I.Y. and M.M.S. acknowledge support from the Australian Research Council Discovery grants DP140101888, DP170100511 and DP230100709. N.C. R. and C.D.S. acknowledge PhD Studentship support from the EPSRC Doctoral Training Partnership and the University of York. P.C., M.H.R. and I.Y. acknowledge generous allocation of high‐performance computing resources by the Australian national computational infrastructure facilities (NCMAS grant e87) and Melbourne Bioinformatics. M.M.S. acknowledges support from the EPSRC programme grant “Advanced Functional Materials” (EP/M020398/1). For the purpose of open access, the author(s) has applied a Creative Commons Attribution (CC BY) licence to any Author Accepted Manuscript version arising. We thank Dr Yiyang Lin for help with Matrix‐Assisted Laser Desorption/Ionization (MALDI) experiments. Publisher Copyright: © 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.

PY - 2024/3/4

Y1 - 2024/3/4

N2 - 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.

AB - 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.

KW - bioconjugation

KW - FRET

KW - liposomes

KW - molecular dynamics

KW - SPAAC

UR - http://www.scopus.com/inward/record.url?scp=85186488646&partnerID=8YFLogxK

U2 - 10.1002/anie.202314786

DO - 10.1002/anie.202314786

M3 - Article

AN - SCOPUS:85186488646

SN - 1433-7851

JO - Angewandte Chemie - International Edition

JF - Angewandte Chemie - International Edition

M1 - e202314786

ER -