Modulating membrane fusion through the design of fusogenic DNA circuits and bilayer composition.
Modulating membrane fusion through the design of fusogenic DNA circuits and bilayer composition.
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作者：
膜融合是与许多生物过程相关的普遍现象，并且代表基于脂质体的药物递送策略中的关键步骤。因此，更精确地控制膜融合途径的能力对于下一代纳米医疗解决方案以及更普遍地设计先进的仿生系统（如合成细胞）非常有价值。在这篇文章中，我们提出了由合成DNA构建的融合纳米结构，与以前的解决方案不同，它解锁了调节融合速率的途径，并使其以可溶性DNA分子的存在为条件，从而展示了如何通过简单的基于DNA的分子电路来控制膜融合。然后，我们系统地探讨脂质膜组成，其生物物理特性，并测量融合效率之间的关系，我们的观察到的融合途径中的过渡态的稳定性。最后，我们观察到，特定的脂质组合物导致出现复杂的双层结构的融合产物，如嵌套的形态，这是伴随着生物物理行为的改变。我们的研究结果提供了多种正交策略来编程脂质-膜融合，其利用融合DNA构建体或膜的物理/化学性质的设计，并且因此在某些设计参数受其他因素如材料成本和生物相容性约束的应用中可能是有价值的，因为在生物技术应用中通常是这种情况。控制脂质-膜融合在纳米医学和合成生物学中是有价值的。在这里，我们提供了指导原则，通过使用融合DNA纳米结构和探索脂质组合物对融合效率的影响来编程。
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. Control over lipid-membrane fusion is valuable in nanomedicine and synthetic biology. Here we provide guiding principles to program it by using fusogenic DNA nanostructures and exploring the effect of lipid composition on fusion efficiency.
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DOI：
10.1021/acs.langmuir.8b02271
发表时间：
2018-12-11
期刊：
Langmuir : the ACS journal of surfaces and colloids
影响因子：
--
作者：
Arnott PM;Joshi H;Aksimentiev A;Howorka S
通讯作者：
Howorka S
影响因子：
21.8
作者：
Adamala KP;Martin-Alarcon DA;Guthrie-Honea KR;Boyden ES
通讯作者：
Boyden ES
影响因子：
18.3
作者：
Gunther G;Malacrida L;Jameson DM;Gratton E;Sánchez SA
通讯作者：
Sánchez SA
影响因子：
4.7
作者：
Kaufhold, Will T.;Brady, Ryan A.;Di Michele, Lorenzo
通讯作者：
Di Michele, Lorenzo
影响因子：
3.9
作者：
Caschera, Filippo;Sunami, Takeshi;Yomo, Tetsuya
通讯作者：
Yomo, Tetsuya