Modulating membrane fusion through the design of fusogenic DNA circuits and bilayer composition
File(s)
Published version
Author(s)
Paez Perez, Miguel
Russell, Alasdair
Cicuta, Pietro
Di Michele, Lorenzo
Type
Journal Article
Abstract
Membrane fusion is a ubiquitous phenomenon linked to many biological processes, and represents
a crucial step in liposome-based drug delivery strategies. The ability to control, ever more precisely,
membrane fusion pathways would thus be highly valuable for next generation nano-medical solutions and, more generally, the design of advanced biomimetic systems such as synthetic cells. In
this article, we present fusogenic nanostructures constructed from synthetic DNA which, different
from previous solutions, unlock routes for modulating the rate of fusion and making it conditional
to the presence of soluble DNA molecules, thus demonstrating how membrane fusion can be controlled through simple DNA-based molecular circuits. We then systematically explore the relationship
between lipid-membrane composition, its biophysical properties, and measured fusion efficiency, linking our observations to the stability of transition states in the fusion pathway. Finally, we observe
that specific lipid compositions lead to the emergence of complex bilayer architectures in the fusion products, such as nested morphologies, which are accompanied by alterations in biophysical
behaviour. Our findings provide multiple, orthogonal strategies to program lipid-membrane fusion,
which leverage the design of either the fusogenic DNA constructs or the physico/chemical properties
of the membranes, and could thus be valuable in applications where some design parameters are
constrained by other factors such as material cost and biocompatibility, as it is often the case in
biotechnological applications.
a crucial step in liposome-based drug delivery strategies. The ability to control, ever more precisely,
membrane fusion pathways would thus be highly valuable for next generation nano-medical solutions and, more generally, the design of advanced biomimetic systems such as synthetic cells. In
this article, we present fusogenic nanostructures constructed from synthetic DNA which, different
from previous solutions, unlock routes for modulating the rate of fusion and making it conditional
to the presence of soluble DNA molecules, thus demonstrating how membrane fusion can be controlled through simple DNA-based molecular circuits. We then systematically explore the relationship
between lipid-membrane composition, its biophysical properties, and measured fusion efficiency, linking our observations to the stability of transition states in the fusion pathway. Finally, we observe
that specific lipid compositions lead to the emergence of complex bilayer architectures in the fusion products, such as nested morphologies, which are accompanied by alterations in biophysical
behaviour. Our findings provide multiple, orthogonal strategies to program lipid-membrane fusion,
which leverage the design of either the fusogenic DNA constructs or the physico/chemical properties
of the membranes, and could thus be valuable in applications where some design parameters are
constrained by other factors such as material cost and biocompatibility, as it is often the case in
biotechnological applications.
Date Issued
2022-08-17
Date Acceptance
2022-08-17
Citation
Soft Matter, 2022, 18 (37), pp.7035-7044
ISSN
1744-683X
Publisher
Royal Society of Chemistry
Start Page
7035
End Page
7044
Journal / Book Title
Soft Matter
Volume
18
Issue
37
Copyright Statement
© The Royal Society of Chemistry 2022. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.
License URL
Sponsor
Commission of the European Communities
The Royal Society
Engineering & Physical Science Research Council (EPSRC)
Identifier
https://pubs.rsc.org/en/content/articlelanding/2022/SM/D2SM00863G
Grant Number
851667
UF160152
EP/V048058/1
Subjects
Science & Technology
Physical Sciences
Technology
Chemistry, Physical
Materials Science, Multidisciplinary
Physics, Multidisciplinary
Polymer Science
Chemistry
Materials Science
Physics
PROGRAMMABLE FUSION
VESICLE FUSION
DRUG-DELIVERY
CHAIN-LENGTH
TRANSPORT
LAURDAN
PRODAN
OCCURS
DNA
Lipid Bilayers
Liposomes
Membrane Fusion
Nanostructures
Lipid Bilayers
DNA
Liposomes
Membrane Fusion
Nanostructures
02 Physical Sciences
03 Chemical Sciences
09 Engineering
Chemical Physics
Publication Status
Published
Date Publish Online
2022-08-17