Sprecher
Beschreibung
Membrane fusion is a ubiquitous phenomenon involved in a myriad of biological processes. It represents a crucial step in viral infection, liposome-based drug delivery, and the construction of fully biomimetic synthetic cells. While fusion between cellular membranes is tightly regulated by specialized proteins, reconstituting and controlling the behaviour of these proteins in synthetic systems remains a significant challenge. To address this, DNA-based nanodevices that mimic the activity of fusogenic proteins have been proposed.[1,2]
Here, we introduce minimal DNA structures – dubbed tendrils[3] – which can be easily modified to trigger fusion in response to external stimuli and to modulate fusion kinetics. Importantly, our design effectively decouples the more expensive, fusogenic cholesterol-modified strands from the control circuitry, enabling a plug-and-play strategy for designing DNA fusogens. Leveraging this modular design, we demonstrate control over membrane fusion kinetics (ranging from minutes to hours), logic-gated fusion responses (e.g., NOT, AND, and OR gates), and temperature-triggered fusion.
To demonstrate the applicability of our system in synthetic cell engineering, we encapsulated small unilamellar vesicles (SUVs) within micron-sized giant unilamellar vesicles (GUVs) and decorated both membranes with temperature-sensitive tendrils. Upon heating, fusion exposed the lipids from the encapsulated SUVs to the external solution, effectively mimicking the biological process of antigen presentation.
Altogether, our results highlight the potential of fusogenic DNA nanodevices as programmable tools for reshaping lipid assemblies and directing the behavior of compartmentalized systems, a key requirement in the development of advanced drug delivery systems and biomimetic synthetic cells. The modularity of DNA tendrils will facilitate the integration of other sensing moieties (e.g. aptamers), paving the way for the development of synthetic membrane-trafficking pathways.
[1] Peruzzi et al. Angew. Chemie 2019
[2] Stengel at al. J. Am. Chem. Soc. 2007
[3] Paez-Perez et al. Soft Matter 2022
