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research article

Calcium-triggered fusion of lipid membranes is enabled by amphiphilic nanoparticles

Tahir, Mukarram A.
•
Guven, Zekiye P.
•
Arriaga, Laura R.
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August 4, 2020
Proceedings Of The National Academy Of Sciences Of The United States Of America (PNAS)

Lipid membrane fusion is an essential process for a number of critical biological functions. The overall process is thermodynamically favorable but faces multiple kinetic barriers along the way. Inspired by nature's engineered proteins such as SNAP receptor [soluble N-ethylmale-imide-sensitive factor-attachment protein receptor (SNARE)] complexes or viral fusogenic proteins that actively promote the development of membrane proximity, nucleation of a stalk, and triggered expansion of the fusion pore, here we introduce a synthetic fusogen that can modulate membrane fusion and equivalently prime lipid membranes for calcium-triggered fusion. Our fusogen consists of a gold nanoparticle functionalized with an amphiphilic monolayer of alkanethiol ligands that had previously been shown to fuse with lipid bilayers. While previous efforts to develop synthetic fusogens have only replicated the initial steps of the fusion cascade, we use molecular simulations and complementary experimental techniques to demonstrate that these nanoparticles can induce the formation of a lipid stalk and also drive its expansion into a fusion pore upon the addition of excess calcium. These results have important implications in general understanding of stimuli-triggered fusion and the development of synthetic fusogens for biomedical applications.

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Type
research article
DOI
10.1073/pnas.1902597117
Web of Science ID

WOS:000573684400020

Author(s)
Tahir, Mukarram A.
•
Guven, Zekiye P.
•
Arriaga, Laura R.
•
Tinao, Berta
•
Yang, Yu-Sang Sabrina
•
Bekdemir, Ahmet  
•
Martin, Jacob T.
•
Bhanji, Alisha N.
•
Irvine, Darrell
•
Stellacci, Francesco  
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Date Issued

2020-08-04

Publisher

National Academy of Sciences

Published in
Proceedings Of The National Academy Of Sciences Of The United States Of America (PNAS)
Volume

117

Issue

31

Start page

18470

End page

18476

Subjects

Multidisciplinary Sciences

•

Science & Technology - Other Topics

•

membrane fusion

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nanoparticles

•

proteins

•

drug delivery

•

snare

•

stalk

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energy

•

energetics

•

curvature

•

interplay

•

pathway

•

model

Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
SUNMIL  
Available on Infoscience
October 15, 2020
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/172484
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