Modulating membrane fusion through the design of fusogenic DNA circuits and bilayer composition.
Soft Matter
; 18(37): 7035-7044, 2022 Sep 28.
Article
em En
| MEDLINE
| ID: mdl-36000473
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Nanoestruturas
/
Fusão de Membrana
Idioma:
En
Revista:
Soft Matter
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Reino Unido