Multiple Intermediates in the Detergent-Induced Fusion of Lipid Vesicles

Lara Dresser; Casper Kunstmann; Donato Conteduca; Christopher  Hofmair; Nathan Smith; Laura Alice Clark; Steven David Johnson; J. Carlos Penedo; Mark Christian Leake; Steven Quinn

doi:10.1038/s43246-024-00628-8

Multiple Intermediates in the Detergent-Induced Fusion of Lipid Vesicles

Lara Dresser, Casper Kunstmann, Donato Conteduca, Christopher Hofmair, Nathan Smith, Laura Alice Clark, Steven David Johnson, J. Carlos Penedo, Mark Christian Leake, Steven Quinn^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

Detergent-induced vesicle interactions, critical for applications including virus inactivation, varies according to the detergent type and membrane composition, but the underlying mechanistic details remain underexplored. Here, we use a lipid mixing assay based on Förster resonance energy transfer (FRET), and single-vesicle characterization approaches to identify that sub-micron-sized vesicles are induced to fuse by the non-ionic detergent Triton-X-100. We demonstrate that the process is a multi-step mechanism, characterized by discrete values of FRET efficiency between membrane-embedded fluorophores, and involves permeabilization, vesicle docking, hemi-fusion and full lipid mixing at sub-solubilizing detergent concentrations. We also dissect the kinetics of vesicle fusion to surface-tethered vesicles using a label-free quartz-crystal microbalance with dissipation monitoring approach, opening a platform for biotechnology applications. The presented strategies provide mechanistic insight into the dynamics of vesicle fusion and have implications for applications including drug delivery and sensor development where transport and manipulation of encapsulated cargo is essential.

Original language	English
Article number	195
Number of pages	12
Journal	Communications Materials
Volume	5
DOIs	https://doi.org/10.1038/s43246-024-00628-8
Publication status	Published - 19 Sept 2024

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10.1038/s43246-024-00628-8Licence: CC BY

Multiple intermediates in the detergent-induced fusion of lipid vesicles.
© The Author(s) 2024
Final published version, 3.65 MBLicence: CC BY

Cite this

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title = "Multiple Intermediates in the Detergent-Induced Fusion of Lipid Vesicles",

abstract = "Detergent-induced vesicle interactions, critical for applications including virus inactivation, varies according to the detergent type and membrane composition, but the underlying mechanistic details remain underexplored. Here, we use a lipid mixing assay based on F{\"o}rster resonance energy transfer (FRET), and single-vesicle characterization approaches to identify that sub-micron-sized vesicles are induced to fuse by the non-ionic detergent Triton-X-100. We demonstrate that the process is a multi-step mechanism, characterized by discrete values of FRET efficiency between membrane-embedded fluorophores, and involves permeabilization, vesicle docking, hemi-fusion and full lipid mixing at sub-solubilizing detergent concentrations. We also dissect the kinetics of vesicle fusion to surface-tethered vesicles using a label-free quartz-crystal microbalance with dissipation monitoring approach, opening a platform for biotechnology applications. The presented strategies provide mechanistic insight into the dynamics of vesicle fusion and have implications for applications including drug delivery and sensor development where transport and manipulation of encapsulated cargo is essential.",

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T1 - Multiple Intermediates in the Detergent-Induced Fusion of Lipid Vesicles

AU - Dresser, Lara

AU - Kunstmann, Casper

AU - Conteduca, Donato

AU - Hofmair, Christopher

AU - Smith, Nathan

AU - Clark, Laura Alice

AU - Johnson, Steven David

AU - Penedo, J. Carlos

AU - Leake, Mark Christian

AU - Quinn, Steven

PY - 2024/9/19

Y1 - 2024/9/19

N2 - Detergent-induced vesicle interactions, critical for applications including virus inactivation, varies according to the detergent type and membrane composition, but the underlying mechanistic details remain underexplored. Here, we use a lipid mixing assay based on Förster resonance energy transfer (FRET), and single-vesicle characterization approaches to identify that sub-micron-sized vesicles are induced to fuse by the non-ionic detergent Triton-X-100. We demonstrate that the process is a multi-step mechanism, characterized by discrete values of FRET efficiency between membrane-embedded fluorophores, and involves permeabilization, vesicle docking, hemi-fusion and full lipid mixing at sub-solubilizing detergent concentrations. We also dissect the kinetics of vesicle fusion to surface-tethered vesicles using a label-free quartz-crystal microbalance with dissipation monitoring approach, opening a platform for biotechnology applications. The presented strategies provide mechanistic insight into the dynamics of vesicle fusion and have implications for applications including drug delivery and sensor development where transport and manipulation of encapsulated cargo is essential.

AB - Detergent-induced vesicle interactions, critical for applications including virus inactivation, varies according to the detergent type and membrane composition, but the underlying mechanistic details remain underexplored. Here, we use a lipid mixing assay based on Förster resonance energy transfer (FRET), and single-vesicle characterization approaches to identify that sub-micron-sized vesicles are induced to fuse by the non-ionic detergent Triton-X-100. We demonstrate that the process is a multi-step mechanism, characterized by discrete values of FRET efficiency between membrane-embedded fluorophores, and involves permeabilization, vesicle docking, hemi-fusion and full lipid mixing at sub-solubilizing detergent concentrations. We also dissect the kinetics of vesicle fusion to surface-tethered vesicles using a label-free quartz-crystal microbalance with dissipation monitoring approach, opening a platform for biotechnology applications. The presented strategies provide mechanistic insight into the dynamics of vesicle fusion and have implications for applications including drug delivery and sensor development where transport and manipulation of encapsulated cargo is essential.

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