Department of Chemistry, Institute of Structural Molecular Biology, University College London, London, WC1H 0AJ, UK.
National Engineering Research Center for Colloidal Materials, Shandong University, Jinan, Shandong, 250100, China.
Small. 2024 Oct;20(42):e2404720. doi: 10.1002/smll.202404720. Epub 2024 Aug 20.
DNA nanostructures designed to interact with bilayer membranes are of fundamental interest as they mimic biological cytoskeletons and other membrane-associated proteins for applications in synthetic biology, biosensing, and biological research. Yet, there is limited insight into how the binary interactions are influenced by steric effects produced by 3D geometries of DNA structures and membranes. This work uses a 3D DNA nanostructure with membrane anchors in four different steric environments to elucidate the interaction with membrane vesicles of varying sizes and different local bilayer morphology. It is found that interactions are significantly affected by the steric environments of the anchors -often against predicted accessibility- as well as local nanoscale morphology of bilayers rather than on the usually considered global vesicle size. Furthermore, anchor-mediated bilayer interactions are co-controlled by weak contacts with non-lipidated DNA regions, as showcased by pioneering size discrimination between 50 and 200 nm vesicles. This study extends DNA nanotechnology to controlled bilayer interactions and can facilitate the design of nanodevices for vesicle-based diagnostics, biosensing, and protocells.
设计用于与双层膜相互作用的 DNA 纳米结构具有重要意义，因为它们模拟了生物细胞骨架和其他与膜相关的蛋白质，可应用于合成生物学、生物传感和生物学研究。然而，人们对二元相互作用如何受到 DNA 结构和膜的 3D 几何形状产生的空间位阻的影响知之甚少。这项工作使用具有四种不同空间位阻环境的膜锚定的 3D DNA 纳米结构，阐明了与不同大小和不同局部双层形态的膜泡的相互作用。结果发现，相互作用受到锚定的空间位阻环境的显著影响——通常与预测的可及性相悖——以及双层的局部纳米级形态，而不是通常考虑的全局囊泡大小。此外，锚介导的双层相互作用受到与非脂化 DNA 区域的弱相互作用的共同控制，这一点通过在 50 和 200nm 囊泡之间进行开创性的大小区分得到了展示。这项研究将 DNA 纳米技术扩展到了对双层相互作用的控制，并可以促进基于囊泡的诊断、生物传感和原细胞的纳米器件的设计。
